{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:29:45Z","timestamp":1792074585002,"version":"4.4.0"},"reference-count":208,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Fund of Bulgaria","award":["K\u041f-06-H31\/16"],"award-info":[{"award-number":["K\u041f-06-H31\/16"]}]},{"name":"National Science Fund of Bulgaria","award":["K\u041f-06-M61\/5"],"award-info":[{"award-number":["K\u041f-06-M61\/5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endothelial cells are constantly exposed to environmental stress factors that, above a certain threshold, trigger cellular senescence and apoptosis. The altered vascular function affects new vessel formation and endothelial fitness, contributing to the progression of age-related diseases. This narrative review highlights the complex interplay between senescence, oxidative stress, extracellular vesicles, and the extracellular matrix and emphasizes the crucial role of angiogenesis in aging and Alzheimer\u2019s disease. The interaction between the vascular and nervous systems is essential for the development of a healthy brain, especially since neurons are exceptionally dependent on nutrients carried by the blood. Therefore, anomalies in the delicate balance between pro- and antiangiogenic factors and the consequences of disrupted angiogenesis, such as misalignment, vascular leakage and disturbed blood flow, are responsible for neurodegeneration. The implications of altered non-productive angiogenesis in Alzheimer\u2019s disease due to dysregulated Delta-Notch and VEGF signaling are further explored. Additionally, potential therapeutic strategies such as exercise and caloric restriction to modulate angiogenesis and vascular aging and to mitigate the associated debilitating symptoms are discussed. Moreover, both the roles of extracellular vesicles in stress-induced senescence and as an early detection marker for Alzheimer\u2019s disease are considered. The intricate relationship between endothelial senescence and angiogenesis provides valuable insights into the mechanisms underlying angiogenesis-related disorders and opens avenues for future research and therapeutic interventions.<\/jats:p>","DOI":"10.3390\/ijms241411344","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T01:43:22Z","timestamp":1689212602000},"page":"11344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Endothelial Senescence and Its Impact on Angiogenesis in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1458-2457","authenticated-orcid":false,"given":"Irina","family":"Georgieva","sequence":"first","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. George Bonchev, Str. Bl. 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-5099","authenticated-orcid":false,"given":"Jana","family":"Tchekalarova","sequence":"additional","affiliation":[{"name":"Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. George Bonchev, Str. Bl. 23, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitar","family":"Iliev","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. George Bonchev, Str. Bl. 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumiana","family":"Tzoneva","sequence":"additional","affiliation":[{"name":"Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. George Bonchev, Str. Bl. 21, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1387\/ijdb.103213sp","article-title":"Signal transduction in vasculogenesis and developmental angiogenesis","volume":"55","year":"2011","journal-title":"Int. J. Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Adair, T.H., and Montani, J.-P. (2010). Angiogenesis, Morgan & Claypool Life Sciences.","DOI":"10.4199\/C00017ED1V01Y201009ISP010"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"960","DOI":"10.3389\/fphys.2017.00960","article-title":"A network model to explore the effect of the micro-environment on endothelial cell behavior during angiogenesis","volume":"8","author":"Weinstein","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"594903","DOI":"10.3389\/fcell.2020.594903","article-title":"In vitro 3D Systems to Model Tumor Angiogenesis and Interactions With Stromal Cells","volume":"8","author":"Monnot","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Stryker, Z.I., Rajabi, M., Davis, P.J., and Mousa, S.A. (2019). Evaluation of angiogenesis assays. Biomedicines, 7.","DOI":"10.3390\/biomedicines7020037"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1161\/CIRCRESAHA.111.246116","article-title":"Effects of aging on angiogenesis","volume":"110","author":"Rosenzweig","year":"2012","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41569-018-0030-z","article-title":"Endothelial dysfunction and angiogenesis impairment in the ageing vasculature","volume":"15","author":"Ungvari","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature10144","article-title":"Molecular mechanisms and clinical applications of angiogenesis","volume":"473","author":"Carmeliet","year":"2011","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1159\/000477402","article-title":"Pro-Angiogenesis Therapy and Aging: A Mini-Review","volume":"63","author":"Ambrose","year":"2017","journal-title":"Gerontology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1161\/01.STR.14.6.924","article-title":"Cerebral amyloid angiopathy: Incidence and complications in the aging brain. II. The distribution of amyloid vascular changes","volume":"14","author":"Vinters","year":"1983","journal-title":"Stroke"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8453","DOI":"10.1523\/JNEUROSCI.23-24-08453.2003","article-title":"Age-Dependent Cerebrovascular Abnormalities and Blood Flow Disturbances in APP23 Mice Modeling Alzheimer\u2019s Disease","volume":"23","author":"Beckmann","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.15252\/embr.201439245","article-title":"Senescence and apoptosis: Dueling or complementary cell fates?","volume":"15","author":"Childs","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_13","unstructured":"Singh, C., Pfeifer, C.G., and Jefferies, W.A. (2017). Physiologic and Pathologic Angiogenesis-Signaling Mechanisms and Targeted Therapy, BoD\u2013Books on Demand."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00702-011-0684-8","article-title":"Evidence for Angiogenesis in Parkinson\u2019s disease, Incidental Lewy Body disease, and Progressive Supranuclear Palsy","volume":"119","author":"Bradaric","year":"2012","journal-title":"J. Neural Transm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1038\/mt.2013.132","article-title":"Dose-dependent Neuroprotection of VEGF165 in Huntington\u2019s DiseaseStriatum","volume":"21","author":"Ellison","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/jnc.15030","article-title":"Amyloid-\u03b2 oligomers in cellular models of Alzheimer\u2019s disease","volume":"155","author":"Fontana","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41583-019-0132-6","article-title":"Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease","volume":"20","author":"Butterfield","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/alzrt230","article-title":"Adjusting the compass: New insights into the role of angiogenesis in Alzheimer\u2019s disease","volume":"5","author":"Jefferies","year":"2013","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tchekalarova, J., and Tzoneva, R. (2023). Oxidative Stress and Aging as Risk Factors for Alzheimer\u2019s Disease and Parkinson\u2019s Disease: The Role of the Antioxidant Melatonin. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24033022"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tadokoro, K., Ohta, Y., Inufusa, H., Loon, A.F.N., and Abe, K. (2020). Prevention of Cognitive Decline in Alzheimer\u2019s Disease by Novel Antioxidative Supplements. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061974"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/nature04481","article-title":"From angiogenesis to neuropathology","volume":"438","author":"Greenberg","year":"2005","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.brainresbull.2022.05.015","article-title":"Morphogenesis of vascular and neuronal networks and the relationships between their remodeling processes","volume":"186","author":"Ribatti","year":"2022","journal-title":"Brain Res. Bull."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","article-title":"The serial cultivation of human diploid cell strains","volume":"25","author":"Hayflick","year":"1961","journal-title":"Exp. Cell Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6829","DOI":"10.18632\/aging.204248","article-title":"New hallmarks of ageing: A 2022 Copenhagen ageing meeting summary","volume":"14","author":"Lautrup","year":"2022","journal-title":"Aging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3389\/fcell.2021.645593","article-title":"Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype","volume":"9","author":"Kumari","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-022-00906-w","article-title":"Endothelial senescence in vascular diseases: Current understanding and future opportunities in senotherapeutics","volume":"55","author":"Han","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_28","first-page":"1646","article-title":"Senescence and Apoptosis During in vitro Embryo Development in a Bovine Model","volume":"8","author":"Gimeno","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e72449","DOI":"10.7554\/eLife.72449","article-title":"The right time for senescence","volume":"10","author":"Jacinto","year":"2021","journal-title":"Elife"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"148","DOI":"10.29173\/hsi304","article-title":"The information theory of aging: Hacking immortality?","volume":"11","author":"Vujin","year":"2020","journal-title":"Health Sci. Inq."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/0531-5565(92)90068-B","article-title":"The telomere hypothesis of cellular aging","volume":"27","author":"Harley","year":"1992","journal-title":"Exp. Gerontol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/geronj\/11.3.298","article-title":"Aging: A theory based on free radical and radiation chemistry","volume":"11","author":"Harman","year":"1956","journal-title":"J. Gerontol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41586-020-2975-4","article-title":"Reprogramming to recover youthful epigenetic information and restore vision","volume":"588","author":"Lu","year":"2020","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.cell.2022.12.027","article-title":"Loss of epigenetic information as a cause of mammalian aging","volume":"186","author":"Yang","year":"2023","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e71624","DOI":"10.7554\/eLife.71624","article-title":"Multi-omic rejuvenation of human cells by maturation phase transient reprogramming","volume":"11","author":"Gill","year":"2022","journal-title":"Elife"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.molcel.2018.02.016","article-title":"Protein Dynamics in Complex DNA Lesions","volume":"69","author":"Aleksandrov","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/s41556-022-00991-z","article-title":"An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory","volume":"24","author":"Lanna","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"38540","DOI":"10.1074\/jbc.M202671200","article-title":"Expression of human telomerase (hTERT) does not prevent stress-induced senescence in normal human fibroblasts but protects the cells from stress-induced apoptosis and necrosis","volume":"277","author":"Gorbunova","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1006\/excr.2001.5182","article-title":"Uncoupling the Senescent Phenotype from Telomere Shortening in Hydrogen Peroxide-Treated Fibroblasts","volume":"265","author":"Chen","year":"2001","journal-title":"Exp. Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kirsch, V., Ramge, J.M., Schoppa, A., Ignatius, A., and Riegger, J. (2022). In Vitro Characterization of Doxorubicin-Mediated Stress-Induced Premature Senescence in Human Chondrocytes. Cells, 11.","DOI":"10.3390\/cells11071106"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1113\/EP089423","article-title":"Extracellular vesicles released from stress-induced prematurely senescent myoblasts impair endothelial function and proliferation","volume":"106","author":"Hettinger","year":"2021","journal-title":"Exp. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106922","DOI":"10.1016\/j.vph.2021.106922","article-title":"Septic shock as a trigger of arterial stress-induced premature senescence: A new pathway involved in the post sepsis long-term cardiovascular complications","volume":"141","author":"Merdji","year":"2021","journal-title":"Vascul. Pharmacol."},{"key":"ref_43","unstructured":"Debacq-Chainiaux, F., Ben Ameur, R., Bauwens, E., Dumortier, E., Toutfaire, M., and Toussaint, O. (2016). Healthy Ageing and Longevity, Springer."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e12146","DOI":"10.1002\/jev2.12146","article-title":"Hypoxia-stimulated ATM activation regulates autophagy-associated exosome release from cancer-associated fibroblasts to promote cancer cell invasion","volume":"10","author":"Xi","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e29903","DOI":"10.4161\/mco.29903","article-title":"ATM activation in hypoxia-causes and consequences","volume":"1","author":"Olcina","year":"2014","journal-title":"Mol. Cell. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.3389\/fcell.2020.599048","article-title":"ATM Kinase-Dependent Regulation of Autophagy: A Key Player in Senescence?","volume":"8","author":"Stagni","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"29662","DOI":"10.1074\/jbc.M110.125138","article-title":"Ataxia Telangiectasia Mutated (ATM)-mediated DNA damage response in oxidative stress-induced vascular endothelial cell senescence","volume":"285","author":"Zhan","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.18632\/aging.102863","article-title":"ATM is a key driver of NF-\u03baB-dependent DNA-damage-induced senescence, stem cell dysfunction and aging","volume":"12","author":"Zhao","year":"2020","journal-title":"Aging"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"724","DOI":"10.15252\/embj.201592862","article-title":"Mitochondria are required for pro-ageing features of the senescent phenotype","volume":"35","author":"Marques","year":"2016","journal-title":"EMBO J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1161\/CIRCRESAHA.118.312498","article-title":"Sirtuins and NAD+ in the Development and Treatment of Metabolic and Cardiovascular Diseases","volume":"123","author":"Kane","year":"2018","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"20946","DOI":"10.18632\/aging.202176","article-title":"Sirtuin 6 deficiency induces endothelial cell senescence via downregulation of forkhead box M1 expression","volume":"12","author":"Lee","year":"2020","journal-title":"Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/hep.32209","article-title":"Shear stress\u2013induced cellular senescence blunts liver regeneration through Notch\u2013sirtuin 1\u2013P21\/P16 axis","volume":"75","author":"Duan","year":"2022","journal-title":"Hepatology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/lifemeta\/loac025","article-title":"Sirtuins are not conserved longevity genes","volume":"1","author":"Brenner","year":"2022","journal-title":"Life Metab."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Huang, P., Chen, G., Jin, W., Mao, K., Wan, H., and He, Y. (2022). Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137292"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1101\/gad.625811","article-title":"Senescent cells develop a PARP-1 and nuclear factor-{kappa}B-associated secretome (PNAS)","volume":"25","author":"Ohanna","year":"2011","journal-title":"Genes Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1111\/acel.12461","article-title":"Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice","volume":"15","author":"Gano","year":"2016","journal-title":"Aging Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/neuro.24.004.2009","article-title":"Resveratrol Preserves Cerebrovascular Density and Cognitive Function in Aging Mice","volume":"1","author":"Oomen","year":"2009","journal-title":"Front. Aging Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"H1691","DOI":"10.1152\/ajpheart.00281.2014","article-title":"Sirtuin 1 ablation in endothelial cells is associated with impaired angiogenesis and diastolic dysfunction","volume":"307","author":"Maizel","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1111\/febs.16325","article-title":"p53 in senescence\u2013it\u2019s a marathon not a sprint","volume":"290","author":"Sheekey","year":"2021","journal-title":"FEBS J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s13046-021-02035-0","article-title":"Cellular senescence or stemness: Hypoxia flips the coin","volume":"40","author":"Carnero","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1038\/s41416-018-0066-1","article-title":"Paracrine roles of cellular senescence in promoting tumourigenesis","volume":"118","author":"Apps","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.tcb.2017.07.004","article-title":"Spatial and Temporal Control of Senescence","volume":"27","author":"Ito","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/S0531-5565(01)00105-X","article-title":"Replicative senescence of human endothelial cells in vitro involves G1 arrest, polyploidization and senescence-associated apoptosis","volume":"36","author":"Wagner","year":"2001","journal-title":"Exp. Gerontol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.freeradbiomed.2017.04.019","article-title":"Ionizing radiation induces long-term senescence in endothelial cells through mitochondrial respiratory complex II dysfunction and superoxide generation","volume":"108","author":"Lafargue","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1007\/PL00007269","article-title":"Age-dependent impairment of coronary collateral development in humans","volume":"15","author":"Nakae","year":"2000","journal-title":"Heart Vessels"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1161\/CIRCRESAHA.118.311378","article-title":"Mechanisms of vascular aging","volume":"123","author":"Ungvari","year":"2018","journal-title":"Circ. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1161\/01.RES.0000125295.43813.1F","article-title":"Age-Related Changes in Vascular Endothelial Growth Factor Dependency and Angiopoietin-1-Induced Plasticity of Adult Blood Vessels","volume":"94","author":"Baffert","year":"2004","journal-title":"Circ. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1210\/me.2013-1405","article-title":"Aging Impairs VEGF-Mediated, Androgen-Dependent Regulation of Angiogenesis","volume":"28","author":"Lecce","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3389\/fgene.2015.00112","article-title":"Age-related vascular stiffening: Causes and consequences","volume":"6","author":"Kohn","year":"2015","journal-title":"Front. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/s42003-021-02285-w","article-title":"Integration of substrate- and flow-derived stresses in endothelial cell mechanobiology","volume":"4","author":"Dessalles","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"18209","DOI":"10.1038\/s41598-019-54336-2","article-title":"Subendothelial stiffness alters endothelial cell traction force generation while exerting a minimal effect on the transcriptome","volume":"9","author":"Bastounis","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41551-022-00964-5","article-title":"Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues","volume":"7","author":"Spang","year":"2022","journal-title":"Nat. Biomed. Eng."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41569-019-0239-5","article-title":"Endothelial responses to shear stress in atherosclerosis: A novel role for developmental genes","volume":"17","author":"Souilhol","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1161\/01.CIR.103.20.2508","article-title":"Temporal Gradients in Shear, but Not Spatial Gradients, Stimulate Endothelial Cell Proliferation","volume":"103","author":"White","year":"2001","journal-title":"Circulation"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"9385","DOI":"10.1073\/pnas.170282597","article-title":"Molecular mechanism of endothelial growth arrest by laminar shear stress","volume":"97","author":"Lin","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1161\/ATVBAHA.114.303415","article-title":"Disturbed flow promotes endothelial senescence via a p53-dependent pathway","volume":"34","author":"Warboys","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/j.jbiomech.2004.09.030","article-title":"Molecular basis of the effects of shear stress on vascular endothelial cells","volume":"38","author":"Li","year":"2005","journal-title":"J. Biomech."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"H945","DOI":"10.1152\/ajpheart.1985.248.6.H945","article-title":"Effect of cell turnover and leaky junctions on arterial macromolecular transport","volume":"248","author":"Weinbaum","year":"1985","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1038\/srep04681","article-title":"Brain microvascular endothelial cells resist elongation due to curvature and shear stress","volume":"4","author":"Ye","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.bpj.2013.11.4502","article-title":"Microvascular Endothelial Cells Migrate Upstream and Align Against the Shear Stress Field Created by Impinging Flow","volume":"106","author":"Ostrowski","year":"2014","journal-title":"Biophys. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1007\/s10439-011-0267-8","article-title":"High Fluid Shear Stress and Spatial Shear Stress Gradients Affect Endothelial Proliferation, Survival, and Alignment","volume":"39","author":"Dolan","year":"2011","journal-title":"Ann. Biomed. Eng."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5476","DOI":"10.1038\/s41467-020-19308-5","article-title":"Marcksl1 modulates endothelial cell mechanoresponse to haemodynamic forces to control blood vessel shape and size","volume":"11","author":"Kondrychyn","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1021\/acs.nanolett.1c00064","article-title":"Mechanical Fingerprint of Senescence in Endothelial Cells","volume":"21","author":"Chala","year":"2021","journal-title":"Nano Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1182\/blood-2005-06-2326","article-title":"Shear stress affects the intracellular distribution of eNOS: Direct demonstration by a novel in vivo technique","volume":"106","author":"Cheng","year":"2005","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.3389\/fphys.2018.01668","article-title":"Vascular oxidative stress: Impact and therapeutic approaches","volume":"9","author":"Sena","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"17018","DOI":"10.1073\/pnas.0607873103","article-title":"Endothelial cellular senescence is inhibited by nitric oxide: Implications in atherosclerosis associated with menopause and diabetes","volume":"103","author":"Hayashi","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"882527","DOI":"10.3389\/fphys.2022.882527","article-title":"Basal Vascular Smooth Muscle Cell Tone in eNOS Knockout Mice Can Be Reversed by Cyclic Stretch and Is Independent of Age","volume":"13","author":"Hendrickx","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5318","DOI":"10.1038\/ncomms6318","article-title":"The key role of transient receptor potential melastatin-2 channels in amyloid-\u03b2-induced neurovascular dysfunction","volume":"5","author":"Park","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bpj.2016.05.034","article-title":"Shear-Induced Nitric Oxide Production by Endothelial Cells","volume":"111","author":"Sriram","year":"2016","journal-title":"Biophys. J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1074\/jbc.M307528200","article-title":"Shear stress regulates endothelial nitric-oxide synthase promoter activity through nuclear factor kappaB binding","volume":"279","author":"Davis","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Ghimire, K., Zaric, J., Alday-Parejo, B., Seebach, J., Bousquenaud, M., Stalin, J., Bieler, G., Schnittler, H.J., and R\u00fcegg, C. (2019). MAGI1 Mediates eNOS Activation and NO Production in Endothelial Cells in Response to Fluid Shear Stress. Cells, 8.","DOI":"10.3390\/cells8050388"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1158\/1541-7786.MCR-11-0065","article-title":"Hypoxia and Senescence: The impact of oxygenation on tumor suppression","volume":"9","author":"Welford","year":"2011","journal-title":"Mol. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1161\/01.RES.0000269183.13937.e8","article-title":"Direct evidence of endothelial oxidative stress with aging in humans: Relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB","volume":"100","author":"Donato","year":"2007","journal-title":"Circ. Res."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Yang, W., and Hekimi, S. (2010). A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000556"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1093\/gerona\/gls242","article-title":"Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells","volume":"68","author":"Ungvari","year":"2013","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1242\/jcs.01097","article-title":"Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells","volume":"117","author":"Kurz","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1016\/j.devcel.2022.06.008","article-title":"A ROS-dependent mechanism promotes CDK2 phosphorylation to drive progression through S phase","volume":"57","author":"Kirova","year":"2022","journal-title":"Dev. Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/ncb1024","article-title":"Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts","volume":"5","author":"Parrinello","year":"2003","journal-title":"Nat. Cell Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1006\/excr.1995.1087","article-title":"The effect of low oxygen tension on the in vitro-replicative life span of human diploid fibroblast cells and their transformed derivatives","volume":"217","author":"Saito","year":"1995","journal-title":"Exp. Cell Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/267423a0","article-title":"Low oxygen concentration extends the lifespan of cultured human diploid cells","volume":"267","author":"Packer","year":"1977","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"101167","DOI":"10.1016\/j.arr.2020.101167","article-title":"The geroscience agenda: Toxic stress, hormetic stress, and the rate of aging","volume":"63","author":"Epel","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1182\/blood-2013-01-478065","article-title":"Erythrocytosis: The HIF pathway in control","volume":"122","author":"Franke","year":"2013","journal-title":"Blood"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2147\/HP.S93413","article-title":"The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy","volume":"83","author":"Muz","year":"2015","journal-title":"Hypoxia"},{"key":"ref_104","first-page":"1140","article-title":"Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects","volume":"13","author":"Jiang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1186\/s13046-019-1384-8","article-title":"Hypoxic exosomes facilitate angiogenesis and metastasis in esophageal squamous cell carcinoma through altering the phenotype and transcriptome of endothelial cells","volume":"38","author":"Mao","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.cmet.2016.09.009","article-title":"Reciprocal Regulation between the Circadian Clock and Hypoxia Signaling at the Genome Level in Mammals","volume":"25","author":"Wu","year":"2017","journal-title":"Cell Metab."},{"key":"ref_107","first-page":"20","article-title":"Changes in ischemic stroke occurrence following daylight saving time transitions","volume":"27\u201328","author":"Ruuskanen","year":"2016","journal-title":"Sleep Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.cmet.2016.09.014","article-title":"Rhythmic Oxygen Levels Reset Circadian Clocks through HIF1\u03b1","volume":"25","author":"Adamovich","year":"2017","journal-title":"Cell Metab."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Tzoneva, R., Georgieva, I., Ivanova, N., Uzunova, V., Nenchovska, Z., Apostolova, S., Stoyanova, T., and Tchekalarova, J. (2021). The Role of Melatonin on Behavioral Changes and Concomitant Oxidative Stress in icvA \u03b2 1-42 Rat Model with Pinealectomy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312763"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.cmet.2005.05.001","article-title":"Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing","volume":"1","author":"Guzy","year":"2005","journal-title":"Cell Metab."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41419-021-03640-9","article-title":"The effect of extracellular vesicles on the regulation of mitochondria under hypoxia","volume":"12","author":"Zhang","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"11635","DOI":"10.1038\/ncomms11635","article-title":"HIF-1\u03b1-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity","volume":"7","author":"Semba","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cmet.2016.09.010","article-title":"Circadian Clock Interaction with HIF1\u03b1 Mediates Oxygenic Metabolism and Anaerobic Glycolysis in Skeletal Muscle","volume":"25","author":"Peek","year":"2017","journal-title":"Cell Metab."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.cell.2018.05.009","article-title":"Acid Suspends the Circadian Clock in Hypoxia through Inhibition of mTOR","volume":"174","author":"Walton","year":"2018","journal-title":"Cell"},{"key":"ref_115","first-page":"346783","article-title":"Ceramides in Alzheimer\u2019s Disease: Key Mediators of Neuronal Apoptosis Induced by Oxidative Stress and A \u03b2 Accumulation","volume":"2015","author":"Hof","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"13314","DOI":"10.1073\/pnas.1205690109","article-title":"Hypoxia suppresses conversion from proliferative arrest to cellular senescence","volume":"109","author":"Leontieva","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s10522-020-09876-w","article-title":"The roles of MTOR and miRNAs in endothelial cell senescence","volume":"21","author":"Khor","year":"2020","journal-title":"Biogerontology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1016\/j.molcel.2021.03.018","article-title":"Physiological hypoxia restrains the senescence-associated secretory phenotype via AMPK-mediated mTOR suppression","volume":"81","author":"Wang","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/jnc.13037","article-title":"Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): Analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD","volume":"133","author":"Tramutola","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1096\/fj.08-114256","article-title":"Hyperoxia-induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS","volume":"23","author":"Klimova","year":"2009","journal-title":"FASEB J."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nature03260","article-title":"Conboy, 2005, Nature, Rejuvenecimento celular e nicho.pdf","volume":"433","author":"Conboy","year":"2005","journal-title":"Nature"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/nm.3569","article-title":"Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice","volume":"20","author":"Villeda","year":"2014","journal-title":"Nat. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/s42255-022-00609-6","article-title":"Systemic induction of senescence in young mice after single heterochronic blood exchange","volume":"4","author":"Jeon","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"603","DOI":"10.14348\/molcells.2022.0056","article-title":"The Role of Extracellular Vesicles in Senescence","volume":"45","author":"Oh","year":"2022","journal-title":"Mol. Cells"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1161\/CIRCRESAHA.117.309681","article-title":"Extracellular Vesicles in Angiogenesis","volume":"120","author":"Todorova","year":"2017","journal-title":"Circ. Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"611039","DOI":"10.3389\/fcell.2020.611039","article-title":"Extracellular Vesicles Are Key Regulators of Tumor Neovasculature","volume":"8","author":"Kuriyama","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Olejarz, W., Kubiak-Tomaszewska, G., Chrzanowska, A., and Lorenc, T. (2020). Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165840"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"15287","DOI":"10.1038\/ncomms15287","article-title":"Exosomes maintain cellular homeostasis by excreting harmful DNA from cells","volume":"8","author":"Takahashi","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"4871","DOI":"10.1111\/jcmm.15047","article-title":"Increased production of functional small extracellular vesicles in senescent endothelial cells","volume":"24","author":"Riquelme","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Choi, E.J., Kil, I.S., and Cho, E.G. (2020). Extracellular Vesicles Derived from Senescent Fibroblasts Attenuate the Dermal Effect on Keratinocyte Differentiation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031022"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0002-9440(10)64887-0","article-title":"Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells","volume":"160","author":"Taraboletti","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/cvr\/cvs017","article-title":"VEGF-induced endothelial cell migration requires urokinase receptor (uPAR)-dependent integrin redistribution","volume":"94","author":"Alexander","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"535","DOI":"10.4161\/cam.22243","article-title":"VEGF-initiated angiogenesis and the uPA\/uPAR system","volume":"6","author":"Breuss","year":"2012","journal-title":"Cell Adh. Migr."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"ra117","DOI":"10.1126\/scisignal.aaa2403","article-title":"The interaction of uPAR with VEGFR2 promotes VEGF-induced angiogenesis","volume":"8","author":"Herkenne","year":"2015","journal-title":"Sci. Signal."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"4154","DOI":"10.1182\/blood-2010-09-307694","article-title":"Density enhanced phosphatase-1 down-regulates urokinase receptor surface expression in confluent endothelial cells","volume":"117","author":"Brunner","year":"2011","journal-title":"Blood"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1161\/ATVBAHA.117.309451","article-title":"PAI-1 is a Marker and a Mediator of Senescence","volume":"37","author":"Vaughan","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1182\/blood-2013-02-478925","article-title":"Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells","volume":"121","author":"Smits","year":"2013","journal-title":"Blood"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1161\/ATVBAHA.115.307085","article-title":"Extracellular vesicles activate a CD36-dependent signaling pathway to inhibit microvascular endothelial cell migration and tube formation","volume":"36","author":"Ramakrishnan","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1152\/ajpheart.00265.2005","article-title":"Endothelial microparticles affect angiogenesis in vitro: Role of oxidative stress","volume":"289","author":"Mezentsev","year":"2005","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"5576023","DOI":"10.1155\/2021\/5576023","article-title":"Senescence Osteoblast-Derived Exosome-Mediated miR-139-5p Regulates Endothelial Cell Functions","volume":"2021","author":"Lu","year":"2021","journal-title":"Biomed Res. Int."},{"key":"ref_143","first-page":"764","article-title":"Senescent HUVECs-secreted exosomes trigger endothelial barrier dysfunction in young endothelial cells","volume":"18","author":"Wong","year":"2019","journal-title":"Excli J."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1182\/blood-2007-02-069997","article-title":"Activation of plasminogen into plasmin at the surface of endothelial microparticles: A mechanism that modulates angiogenic properties of endothelial progenitor cells in vitro","volume":"110","author":"Lacroix","year":"2007","journal-title":"Blood"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1152\/ajpendo.00611.2010","article-title":"Endothelium-derived microparticles inhibit angiogenesis in the heart and enhance the inhibitory effects of hypercholesterolemia on angiogenesis","volume":"300","author":"Ou","year":"2011","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"7144","DOI":"10.7150\/thno.59152","article-title":"Plasma-derived DNA containing-extracellular vesicles induce STING-mediated proinflammatory responses in dermatomyositis","volume":"11","author":"Li","year":"2021","journal-title":"Theranostics"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.14336\/AD.2022.0316","article-title":"Role of the cGAS-STING Pathway in Aging-related Endothelial Dysfunction","volume":"13","author":"Yu","year":"2022","journal-title":"Aging Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"14102","DOI":"10.1038\/s41598-019-50681-4","article-title":"The effect of chronic cerebral hypoperfusion on the pathology of Alzheimer\u2019s disease: A positron emission tomography study in rats","volume":"9","author":"Park","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"23964","DOI":"10.1038\/srep23964","article-title":"Chronic cerebral hypoperfusion enhances Tau hyperphosphorylation and reduces autophagy in Alzheimer\u2019s disease mice","volume":"6","author":"Qiu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.stemcr.2021.01.019","article-title":"Adult hippocampal neurogenesis in aging and Alzheimer\u2019s disease","volume":"16","author":"Babcock","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Cameron, D.J., Galvin, C., Alkam, T., Sidhu, H., Ellison, J., Luna, S., and Ethell, D.W. (2012). Alzheimer\u2019s-Related Peptide Amyloid-b Plays a Conserved Role in Angiogenesis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039598"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"E1289","DOI":"10.1073\/pnas.1710329115","article-title":"Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer\u2019s disease","volume":"115","author":"Bennett","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1038\/s41467-021-23337-z","article-title":"Non-productive angiogenesis disassembles A\u00df plaque-associated blood vessels","volume":"12","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0197-4580(01)00285-8","article-title":"Increased intrathecal levels of the angiogenic factors VEGF and TGF-\u03b2 in Alzheimer\u2019s disease and vascular dementia","volume":"23","author":"Tarkowski","year":"2002","journal-title":"Neurobiol. Aging"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"4626","DOI":"10.1096\/fj.201802003R","article-title":"VEGF receptor-1 modulates amyloid \u03b2 1-42 oligomer-induced senescence in brain endothelial cells","volume":"33","author":"Angom","year":"2019","journal-title":"FASEB J."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ijdevneu.2005.11.011","article-title":"Developmental and amyloid plaque-related changes in cerebral cortical capillaries in transgenic Tg2576 Alzheimer mice","volume":"24","author":"Kouznetsova","year":"2006","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"srep02053","DOI":"10.1038\/srep02053","article-title":"VEGF significantly restores impaired memory behavior in Alzheimer\u2019s mice by improvement of vascular survival","volume":"3","author":"Religa","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Jullienne, A., Quan, R., Szu, J.I., Trinh, M.V., Behringer, E.J., and Obenaus, A. (2022). Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer\u2019s Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081967"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3389\/fncel.2020.618986","article-title":"Microvascular Alterations in Alzheimer\u2019s Disease","volume":"14","author":"Steinman","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12950-021-00269-5","article-title":"Role of melatonin in the angiogenesis potential; highlights on the cardiovascular disease","volume":"18","author":"Rahbarghazi","year":"2021","journal-title":"J. Inflamm."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.taap.2017.09.022","article-title":"Melatonin as an angiogenesis inhibitor to combat cancer: Mechanistic evidence","volume":"335","author":"Goradel","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1073\/pnas.0611206104","article-title":"Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting","volume":"104","author":"Lobov","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.cell.2018.02.008","article-title":"Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging","volume":"173","author":"Das","year":"2018","journal-title":"Cell"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1038\/srep01354","article-title":"Cessation of Neoangiogenesis in Alzheimer\u2019s Disease Follows Amyloid-beta Immunization","volume":"3","author":"Biron","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"25800","DOI":"10.1073\/pnas.2008762117","article-title":"Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer\u2019s disease","volume":"117","author":"Lau","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00018-017-2664-0","article-title":"Amyloid precursor protein products concentrate in a subset of exosomes specifically endocytosed by neurons","volume":"75","author":"Laulagnier","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00401-018-1868-1","article-title":"Alzheimer\u2019s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers","volume":"136","author":"Civitelli","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/jnc.15697","article-title":"Extracellular vesicles in the study of Alzheimer\u2019s and Parkinson\u2019s diseases: Methodologies applied from cells to biofluids","volume":"163","author":"Vaz","year":"2022","journal-title":"J. Neurochem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3389\/fnagi.2019.00232","article-title":"Exosome determinants of physiological aging and age-related neurodegenerative diseases","volume":"11","author":"Fenoglio","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3233\/JAD-190656","article-title":"Extracellular Vesicles Isolated from Familial Alzheimer\u2019s Disease Neuronal Cultures Induce Aberrant Tau Phosphorylation in the Wild-Type Mouse Brain","volume":"72","author":"Aulston","year":"2019","journal-title":"J. Alzheimers. Dis."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13195-020-00623-4","article-title":"Alzheimer\u2019s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles","volume":"12","author":"Guo","year":"2020","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/jnc.13514","article-title":"Exosomal cellular prion protein drives fibrillization of amyloid beta and counteracts amyloid beta-mediated neurotoxicity","volume":"137","author":"Falker","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Gabrielli, M., Tozzi, F., Verderio, C., and Origlia, N. (2022). Emerging Roles of Extracellular Vesicles in Alzheimer\u2019s Disease: Focus on Synaptic Dysfunction and Vesicle\u2013Neuron Interaction. Cells, 12.","DOI":"10.3390\/cells12010063"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Lee, S., Mankhong, S., and Kang, J.H. (2019). Extracellular Vesicle as a Source of Alzheimer\u2019s Biomarkers: Opportunities and Challenges. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071728"},{"key":"ref_175","first-page":"1636","article-title":"Insights Into the Proteomic Profiling of Extracellular Vesicles for the Identification of Early Biomarkers of Neurodegeneration","volume":"11","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1111\/bpa.12699","article-title":"Brain-derived and circulating vesicle profiles indicate neurovascular unit dysfunction in early Alzheimer\u2019s disease","volume":"29","author":"Serra","year":"2019","journal-title":"Brain Pathol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"a011452","DOI":"10.1101\/cshperspect.a011452","article-title":"Neurovascular Dysfunction and Faulty Amyloid \u03b2-Peptide Clearance in Alzheimer Disease","volume":"2","author":"Sagare","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"811210","DOI":"10.3389\/fnagi.2021.811210","article-title":"Endothelial Progenitor Cells and Vascular Alterations in Alzheimer\u2019s Disease","volume":"13","author":"Custodia","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nrn3114","article-title":"Neurovascular pathways to neurodegeneration in Alzheimer\u2019s disease and other disorders","volume":"12","author":"Zlokovic","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"a006692","DOI":"10.1101\/cshperspect.a006692","article-title":"Human endothelial progenitor cells","volume":"2","author":"Yoder","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1002\/term.2678","article-title":"Fetal bovine serum-free culture of endothelial progenitor cells-progress and challenges","volume":"12","author":"Bauman","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1161\/01.ATV.0000114236.77009.06","article-title":"Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis","volume":"24","author":"Hur","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1212\/WNL.0b013e3181a711f4","article-title":"Reduced circulating angiogenic cells in Alzheimer disease","volume":"72","author":"Lee","year":"2009","journal-title":"Neurology"},{"key":"ref_184","first-page":"901","article-title":"Endothelial progenitor cells with Alzheimer\u2019s disease","volume":"124","author":"Kong","year":"2011","journal-title":"Chin. Med. J."},{"key":"ref_185","first-page":"590","article-title":"Study of quantity and function of endothelial progenitor cells in peripheral blood of patients with Alzheimer\u2019s disease","volume":"51","author":"Li","year":"2020","journal-title":"J. New Med."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jns.2018.01.019","article-title":"Transplantation of in vitro cultured endothelial progenitor cells repairs the blood-brain barrier and improves cognitive function of APP\/PS1 transgenic AD mice","volume":"387","author":"Zhang","year":"2018","journal-title":"J. Neurol. Sci."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"8772","DOI":"10.1111\/jcmm.15511","article-title":"Secretion of proteins and antibody fragments from transiently transfected endothelial progenitor cells","volume":"24","author":"Heller","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"230791","DOI":"10.1155\/2014\/230791","article-title":"Exercise training could improve age-related changes in cerebral blood flow and capillary vascularity through the upregulation of VEGF and eNOS","volume":"2014","author":"Viboolvorakul","year":"2014","journal-title":"Biomed Res. Int."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Soto, I., Graham, L.C., Richter, H.J., Simeone, S.N., Radell, J.E., and Grabowska, W. (2015). APOE Stabilization by Exercise Prevents Aging Neurovascular Dysfunction and Complement Induction. PLoS Biol., 13.","DOI":"10.1371\/journal.pbio.1002279"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1600-0404.2010.01412.x","article-title":"Physical exercise alleviates debilities of normal aging and Alzheimer \u00d5 s disease","volume":"123","author":"Archer","year":"2011","journal-title":"Acta Neurol. Scand."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"15557","DOI":"10.1038\/ncomms15557","article-title":"Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1","volume":"8","author":"Morland","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2174\/156720206775541787","article-title":"Cerebral Angiogenesis and Expression of Angiogenic Factors in Aging Rats after Exercise","volume":"3","author":"Ding","year":"2006","journal-title":"Curr. Neurovascular Res."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"28239","DOI":"10.3402\/jev.v4.28239","article-title":"Physical exercise induces rapid release of small extracellular vesicles into the circulation","volume":"4","author":"Helmig","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1615820","DOI":"10.1080\/20013078.2019.1615820","article-title":"Platelets, endothelial cells and leukocytes contribute to the exercise-triggered release of extracellular vesicles into the circulation","volume":"8","author":"Brahmer","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"604274","DOI":"10.3389\/fphys.2020.604274","article-title":"Extracellular Vesicles and Exosomes: Insights From Exercise Science","volume":"11","author":"Nederveen","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"H1091","DOI":"10.1152\/ajpheart.00038.2016","article-title":"Advanced age decreases local calcium signaling in endothelium of mouse mesenteric arteries in vivo","volume":"310","author":"Boerman","year":"2016","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/jcp.20955","article-title":"Endothelial cell response to lactate: Implication of PAR modification of VEGF","volume":"211","author":"Kumar","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s10456-012-9282-0","article-title":"Lactate stimulates angiogenesis and accelerates the healing of superficial and ischemic wounds in mice","volume":"15","author":"Porporato","year":"2012","journal-title":"Angiogenesis"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41568-018-0061-0","article-title":"Fasting and cancer: Molecular mechanisms and clinical application","volume":"18","author":"Nencioni","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1159\/000480504","article-title":"Untangling longevity, dauer, and healthspan in Caenorhabditis elegans insulin\/IGF-1-signalling","volume":"64","author":"Ewald","year":"2018","journal-title":"Gerontology"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.cmet.2014.02.009","article-title":"The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice","volume":"19","author":"McMahon","year":"2014","journal-title":"Cell Metab."},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Rajapakse, A.G., Yepuri, G., Carvas, J.M., Stein, S., Matter, C.M., Scerri, I., Ruffieux, J., Montani, J.P., Ming, X.F., and Yang, Z. (2011). Hyperactive S6K1 Mediates Oxidative Stress and Endothelial Dysfunction in Aging: Inhibition by Resveratrol. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019237"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1111\/acel.12103","article-title":"Life-Long Caloric Restriction Reduces Oxidative Stress and Preserves Nitric Oxide Bioavailability and Function in Arteries of Old Mice","volume":"12","author":"Donato","year":"2013","journal-title":"Aging Cell"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/s43587-021-00098-4","article-title":"Autophagy in healthy aging and disease","volume":"1","author":"Aman","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"7177","DOI":"10.1113\/JP272348","article-title":"Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing","volume":"594","author":"Martens","year":"2016","journal-title":"J. Physiol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/s13287-019-1404-9","article-title":"Antioxidants inhibit cell senescence and preserve stemness of adipose tissue-derived stem cells by reducing ROS generation during long-term in vitro expansion","volume":"10","author":"Liao","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/rda.12946","article-title":"Effects of supplementation of medium with different antioxidants during in vitro maturation of bovine oocytes on subsequent embryo production","volume":"52","author":"Sovernigo","year":"2017","journal-title":"Reprod. Domest. Anim."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Guillot, E., Lemay, A., Allouche, M., Vitorino Silva, S., Coppola, H., Sabatier, F., Dignat-George, F., Sarre, A., Peyter, A.C., and Simoncini, S. (2023). Resveratrol Reverses Endothelial Colony-Forming Cell Dysfunction in Adulthood in a Rat Model of Intrauterine Growth Restriction. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119747"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11344\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:11:12Z","timestamp":1760127072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,12]]},"references-count":208,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241411344"],"URL":"https:\/\/doi.org\/10.3390\/ijms241411344","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,12]]}}}