{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:21:30Z","timestamp":1793647290666,"version":"4.5.1"},"reference-count":98,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Immunometabolism"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The endothelium is a crucial regulator of vascular homeostasis by controlling barrier integrity as well acting as an important signal transducer, thereby illustrating that endothelial cells are not inert cells. In the context of atherosclerosis, this barrier function is impaired and endothelial cells become activated, resulting in the upregulation of adhesion molecules, secretion of cytokines and chemokines and internalization of integrins. Finally, this leads to increased vessel permeability, thereby facilitating leukocyte extravasation as well as fostering a pro-inflammatory environment. Additionally, activated endothelial cells can form migrating tip cells and proliferative stalk cells, resulting in the formation of new blood vessels. Emerging evidence has accumulated indicating that cellular metabolism is crucial in fueling these pro-atherosclerotic processes, including neovascularization and inflammation, thereby contributing to plaque progression and altering plaque stability. Therefore, further research is necessary to unravel the complex mechanisms underlying endothelial cell metabolic changes, and exploit this knowledge for finding and developing potential future therapeutic strategies. In this review we discuss the metabolic alterations endothelial cells undergo in the context of inflammation and atherosclerosis and how this relates to changes in endothelial functioning. Finally, we will describe several metabolic targets that are currently being used for therapeutic interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.20900\/immunometab20210020","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T21:05:31Z","timestamp":1621285531000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":23,"title":["Vascular Metabolism as Driver of Atherosclerosis: Linking Endothelial Metabolism to Inflammation"],"prefix":"10.1097","volume":"3","author":[{"given":"Kim E.","family":"Dzobo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie M. 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Circ Res. 2016;118(4):620-36. doi: 10.1161\/CIRCRESAHA.115.306301","DOI":"10.1161\/CIRCRESAHA.115.306301"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"4. Schnitzler JG, Hoogeveen RM, Ali L, Prange KHM, Waissi F, van Weeghel M, et al. Atherogenic Lipoprotein(a) Increases Vascular Glycolysis, Thereby Facilitating Inflammation and Leukocyte Extravasation. Circ Res. 2020;126(10):1346-59. doi: 10.1161\/CIRCRESAHA.119.316206","DOI":"10.1161\/CIRCRESAHA.119.316206"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"5. Bravi L, Dejana E, Lampugnani MG. VE-cadherin at a glance. Cell Tissue Res. 2014;355(3):515-22. doi: 10.1007\/s00441-014-1843-7","DOI":"10.1007\/s00441-014-1843-7"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"6. Gavard J, Gutkind JS. VEGF Controls endothelial-cell permeability promoting \u03b2-arrestin-dependent Endocytosis VE-cadherin. Nat Cell Biol. 2006;8(11):1223-34. doi: 10.1038\/ncb1486","DOI":"10.1038\/ncb1486"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"7. Parma L, Baganha F, Quax PHA, de Vries MR. Plaque angiogenesis and intraplaque hemorrhage in atherosclerosis. Eur J Pharmacol. 2017;816:107-15. doi: 10.1016\/j.ejphar.2017.04.028","DOI":"10.1016\/j.ejphar.2017.04.028"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"8. Virmani R, Kolodgie FD, Burke AP, Finn AV, Gold HK, Tulenko TN, et al. Atherosclerotic plaque progression and vulnerability to rupture: Angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol. 2005;25(10):2054-61. doi: 10.1161\/01.ATV.0000178991.71605.18","DOI":"10.1161\/01.ATV.0000178991.71605.18"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"9. Sedding DG, Boyle EC, Demandt JAF, Sluimer JC, Dutzmann J, Haverich A, et al. Vasa Vasorum Angiogenesis: Key Player in the Initiation and Progression of Atherosclerosis and Potential Target for the Treatment of Cardiovascular Disease. Front Immunol. 2018;9:706. doi: 10.3389\/fimmu.2018.00706","DOI":"10.3389\/fimmu.2018.00706"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"10. Harjes U, Bensaad K, Harris AL. Endothelial cell metabolism and implications for cancer therapy. Br J Cancer. 2012;107(8):1207-12. doi: 10.1038\/bjc.2012.398","DOI":"10.1038\/bjc.2012.398"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"11. Cantelmo AR, Conradi L-C, Brajic A, Goveia J, Kalucka J, Andreas Pircher A, et al. Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy. Cancer Cell. 2016;30(6):968-85. doi: 10.1016\/j.ccell.2016.10.006","DOI":"10.1016\/j.ccell.2016.10.006"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"12. Vaupel P, Schmidberger H, Mayer A. The Warburg effect: essential part of metabolic reprogramming and central contributor to cancer progression. Int J Radiat Biol. 2019;95(7):912-9. doi: 10.1080\/09553002.2019.1589653","DOI":"10.1080\/09553002.2019.1589653"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"13. Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11(5):325-37. doi: 10.1038\/nrc3038","DOI":"10.1038\/nrc3038"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"14. Yvan-Charvet L, Ivanov S. Metabolic reprogramming of macrophages in atherosclerosis: Is it all about cholesterol? J Lipid Atheroscler. 2020;9(2):231-42. doi: 10.12997\/jla.2020.9.2.231","DOI":"10.12997\/jla.2020.9.2.231"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"15. Groh L, Keating ST, Joosten LAB, Netea MG, Riksen NP. Monocyte and macrophage immunometabolism in atherosclerosis. Semin Immunopathol. 2018;40(2):203-14. doi: 10.1007\/s00281-017-0656-7","DOI":"10.1007\/s00281-017-0656-7"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"16. Poels K, Schnitzler JG, Waissi F, Levels JHM, Stroes ESG, Daemen MJAP, et al. Inhibition of PFKFB3 Hampers the Progression of Atherosclerosis and Promotes Plaque Stability. Front Cell Dev Biol. 2020;8. doi: 10.3389\/fcell.2020.581641","DOI":"10.3389\/fcell.2020.581641"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"17. Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, et al. In Vivo 18F-Fluorodeoxyglucose Positron Emission Tomography Imaging Provides a Noninvasive Measure of Carotid Plaque Inflammation in Patients. J Am Coll Cardiol. 2006;48(9):1818-24. doi: 10.1016\/j.jacc.2006.05.076","DOI":"10.1016\/j.jacc.2006.05.076"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"18. Schnitzler JG, Hoogeveen RM, Ali L, Prange KHM, Waissi F, Michel van Weeghel M, et al. Atherogenic Lipoprotein(a) Increases Vascular Glycolysis, Thereby Facilitating Inflammation and Leukocyte Extravasation. Circ Res. 2020 May 8;126(10):1346-59. doi: 10.1161\/circresaha.119.316206","DOI":"10.1161\/CIRCRESAHA.119.316206"},{"key":"ref18","unstructured":"19. Vallabhajosula S, Fuster V. Atherosclerosis: Imaging techniques and the evolving role of nuclear medicine. J Nucl Med. 1997;38(11):1788-96."},{"key":"ref19","unstructured":"20. Mochizuki T, Tsukamoto E, Kuge Y, Kanegae K, Zhao S, Hikosaka K, et al. FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. J Nucl Med. 2001;42(10):1551-5."},{"key":"ref20","unstructured":"21. Okazumi S, Isono K, Enomoto K, Kikuchi T, Ozaki M, Yamamoto H, et al. Evaluation of liver tumors using fluorine-18-fluorodeoxyglucose PET: Characterization of tumor and assessment of effect of treatment. J Nucl Med. 1992;33(3):333-9."},{"key":"ref21","doi-asserted-by":"publisher","unstructured":"22. Sarrazy V, Viaud M, Westerterp M, Ivanov S, Giorgetti-Peraldi S, Guinamard R, et al. Disruption of Glut1 in Hematopoietic Stem Cells Prevents Myelopoiesis and Enhanced Glucose Flux in Atheromatous Plaques of ApoE(\u2212\/\u2212) Mice. Circ Res. 2016;118(7):1062-77. doi: 10.1161\/CIRCRESAHA.115.307599","DOI":"10.1161\/CIRCRESAHA.115.307599"},{"key":"ref22","doi-asserted-by":"publisher","unstructured":"23. Tomas L, Edsfeldt A, Mollet IG, Matic LP, Prehn C, Adamski J, et al. Altered metabolism distinguishes high-risk from stable carotid atherosclerotic plaques. Eur Heart J. 2018;39(24):2301-10. doi: 10.1093\/eurheartj\/ehy124","DOI":"10.1093\/eurheartj\/ehy124"},{"issue":"2","key":"ref23","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/0167-4889(83)90084-8","article-title":"Metabolic properties of freshly isolated bovine endothelial cells","volume":"762","author":"Dobrina","year":"1983","unstructured":"24. Dobrina A, Rossi F. Metabolic properties of freshly isolated bovine endothelial cells. Biochim Biophys Acta. 1983;762(2):295-301.","journal-title":"Biochim Biophys Acta"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"25. Kr\u00fctzfeldt A, Spahr R, Mertens S, Siegmund B, Piper HM. Metabolism of exogenous substrates by coronary endothelial cells in culture. J Mol Cell Cardiol. 1990;22(12):1393-1404. doi: 10.1016\/0022-2828(90)90984-A","DOI":"10.1016\/0022-2828(90)90984-A"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"26. De Bock K, Georgiadou M, Carmeliet P. Role of endothelial cell metabolism in vessel sprouting. Cell Metab. 2013;18(5):634-47. doi: 10.1016\/j.cmet.2013.08.001","DOI":"10.1016\/j.cmet.2013.08.001"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"27. Mertens S, Noll T, Spahr R, Krutzfeldt A, Piper HM. Energetic response of coronary endothelial cells to hypoxia. Am J Physiol Hear Circ Physiol. 1990 Mar;258(3 Pt 2):H689-94. doi: 10.1152\/ajpheart.1990.258.3.h689","DOI":"10.1152\/ajpheart.1990.258.3.H689"},{"key":"ref27","doi-asserted-by":"publisher","unstructured":"28. Oldendorf WH, Cornford ME, Brown WJ. The large apparent work capability of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol. 1977;1(5):409-17. doi: 10.1002\/ana.410010502","DOI":"10.1002\/ana.410010502"},{"key":"ref28","doi-asserted-by":"publisher","unstructured":"29. Kolodgie FD, Burke AP, Farb A, Gold HK, Yuan J, Narula J, et al. The thin-cap fibroatheroma: A type of vulnerable plaque the major precursor lesion to acute coronary syndromes. Curr Opin Cardiol. 2001;16(5):285-92. doi: 10.1097\/00001573-200109000-00006","DOI":"10.1097\/00001573-200109000-00006"},{"key":"ref29","doi-asserted-by":"publisher","unstructured":"30. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003;161(6):1163-77. doi: 10.1083\/jcb.200302047","DOI":"10.1083\/jcb.200302047"},{"key":"ref30","doi-asserted-by":"publisher","unstructured":"31. De Smet F, Segura I, De Bock K, Hohensinner PJ, Carmeliet P. Mechanisms of vessel branching: Filopodia on endothelial tip cells lead the way. Arterioscler Thromb Vasc Biol. 2009;29(5):639-49. doi: 10.1161\/ATVBAHA.109.185165","DOI":"10.1161\/ATVBAHA.109.185165"},{"key":"ref31","doi-asserted-by":"publisher","unstructured":"32. Adams RH, Eichmann A. Axon guidance molecules in vascular patterning. Cold Spring Harb Perspect Biol. 2010;2(5):1-18. doi: 10.1101\/cshperspect.a001875","DOI":"10.1101\/cshperspect.a001875"},{"key":"ref32","doi-asserted-by":"publisher","unstructured":"33. Bierhansl L, Conradi LC, Treps L, Dewerchin M, Carmeliet P. Central role of metabolism in endothelial cell function and vascular disease. Physiology. 2017;32(2):126-40. doi: 10.1152\/physiol.00031.2016","DOI":"10.1152\/physiol.00031.2016"},{"key":"ref33","doi-asserted-by":"publisher","unstructured":"34. Goveia J, Stapor P, Carmeliet P. Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease. EMBO Mol Med. 2014;6(9):1105-20. doi: 10.15252\/emmm.201404156","DOI":"10.15252\/emmm.201404156"},{"key":"ref34","doi-asserted-by":"publisher","unstructured":"35. De Bock K, Georgiadou M, Schoors S, Kuchnio A, Wong BW, Cantelmo AR, et al. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell. 2013;154(3):651-63. doi: 10.1016\/j.cell.2013.06.037","DOI":"10.1016\/j.cell.2013.06.037"},{"key":"ref35","doi-asserted-by":"publisher","unstructured":"36. Jiang H, Zou Y, Zhao J, Li X, Yang S, Zhou X, et al. Pyruvate Kinase M2 Mediates Glycolysis in the Lymphatic Endothelial Cells and Promotes the Progression of Lymphatic Malformations. Am J Pathol. 2021;191(1):204-15. doi: 10.1016\/j.ajpath.2020.10.003","DOI":"10.1016\/j.ajpath.2020.10.003"},{"key":"ref36","doi-asserted-by":"publisher","unstructured":"37. G\u00f3mez-Escudero J, Clemente C, Garc\u00eda-Weber D, Ac\u00edn-P\u00e9rez R, Mill\u00e1n J, Enr\u00edquez JA, et al. PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production. Sci Rep. 2019;9(1):1-18. doi: 10.1038\/s41598-019-50866-x","DOI":"10.1038\/s41598-019-50866-x"},{"key":"ref37","doi-asserted-by":"publisher","unstructured":"38. Yetkin-Arik B, Vogels IMC, Nowak-Sliwinska P, Weiss A, Houtkooper RH, Van Noorden CJF, et al. The role of glycolysis and mitochondrial respiration in the formation and functioning of endothelial tip cells during angiogenesis. Sci Rep. 2019;9(1):1-14. doi: 10.1038\/s41598-019-48676-2","DOI":"10.1038\/s41598-019-48676-2"},{"key":"ref38","doi-asserted-by":"publisher","unstructured":"39. Diebold LP, Gil HJ, Gao P, Martinez CA, Weinberg SE, Chandel NS. Mitochondrial complex III is necessary for endothelial cell proliferation during angiogenesis. Nat Metab. 2019;1(1):158-71. doi: 10.1038\/s42255-018-0011-x","DOI":"10.1038\/s42255-018-0011-x"},{"key":"ref39","doi-asserted-by":"publisher","unstructured":"40. Lapel M, Weston P, Strassheim D, Karoor V, Burns N, Lyubchenko T, et al. Glycolysis and oxidative phosphorylation are essential for purinergic receptor-mediated angiogenic responses in vasa vasorum endothelial cells. Am J Physiol Cell Physiol. 2017;312(1):C56-70. doi: 10.1152\/ajpcell.00250.2016","DOI":"10.1152\/ajpcell.00250.2016"},{"key":"ref40","doi-asserted-by":"publisher","unstructured":"41. Schoors S, Bruning U, Missiaen R, Queiroz KC, Borgers G, Elia I, et al. Fatty acid carbon is essential for dNTP synthesis in endothelial cells. Nature. 2015;520(7546):192-7. doi: 10.1038\/nature14362","DOI":"10.1038\/nature14362"},{"key":"ref41","doi-asserted-by":"publisher","unstructured":"42. Chen PY, Qin L, Baeyens N, Li G, Afolabi T, Budatha M, et al. Endothelial-to-mesenchymal transition drives atherosclerosis progression. J Clin Invest. 2015;125(12):4514-28. doi: 10.1172\/JCI82719","DOI":"10.1172\/JCI82719"},{"key":"ref42","doi-asserted-by":"publisher","unstructured":"43. Evrard SM, Lecce L, Michelis KC, Nomura-Kitabayashi A, Pandey G, Purushothaman KR, et al. Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability. Nat Commun. 2016;7(1):1-16. doi: 10.1038\/ncomms11853","DOI":"10.1038\/ncomms11853"},{"key":"ref43","doi-asserted-by":"publisher","unstructured":"44. Xiong J, Kawagishi H, Yan Y, Liu J, Wells QS, Edmunds LR, et al. A Metabolic Basis for Endothelial-to-Mesenchymal Transition. Mol Cell. 2018;69(4):689-98.e7. doi: 10.1016\/j.molcel.2018.01.010","DOI":"10.1016\/j.molcel.2018.01.010"},{"key":"ref44","doi-asserted-by":"publisher","unstructured":"45. Feng S, Bowden N, Fragiadaki M, Souilhol C, Hsiao S, Mahmoud M, et al. Mechanical activation of hypoxia-inducible factor 1a drives endothelial dysfunction at atheroprone sites. Arterioscler Thromb Vasc Biol. 2017;37(11):2087-101. doi: 10.1161\/ATVBAHA.117.309249","DOI":"10.1161\/ATVBAHA.117.309249"},{"key":"ref45","doi-asserted-by":"publisher","unstructured":"46. Sun L, Zhao M, Liu A, Lv M, Zhang J, Li Y, et al. Shear Stress Induces Phenotypic Modulation of Vascular Smooth Muscle Cells via AMPK\/mTOR\/ULK1-Mediated Autophagy. Cell Mol Neurobiol. 2018;38(2):541-8. doi: 10.1007\/s10571-017-0505-1","DOI":"10.1007\/s10571-017-0505-1"},{"key":"ref46","doi-asserted-by":"publisher","unstructured":"47. Vion AC, Kheloufi M, Hammoutene A, Poisson J, Lasselin J, Devue C, et al. Autophagy is required for endothelial cell alignment and atheroprotection under physiological blood flow. Proc Natl Acad Sci U S A. 2017;114(41):E8675-84. doi: 10.1073\/pnas.1702223114","DOI":"10.1073\/pnas.1702223114"},{"key":"ref47","doi-asserted-by":"publisher","unstructured":"48. Doddaballapur A, Michalik KM, Manavski Y, Lucas T, Houtkooper RH, You X, et al. Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3. Arterioscler Thromb Vasc Biol. 2015;35(1):137-45. doi: 10.1161\/ATVBAHA.114.304277","DOI":"10.1161\/ATVBAHA.114.304277"},{"key":"ref48","doi-asserted-by":"publisher","unstructured":"49. Wang G, Kostidis S, Tiemeier GL, Sol WMPJ, de Vries MR, Giera M, et al. Shear stress regulation of endothelial glycocalyx structure is determined by glucobiosynthesis. Arterioscler Thromb Vasc Biol. 2020;40(2):350-64. doi: 10.1161\/ATVBAHA.119.313399","DOI":"10.1161\/ATVBAHA.119.313399"},{"key":"ref49","doi-asserted-by":"publisher","unstructured":"50. Wilhelm K, Happel K, Eelen G, Schoors S, Oellerich MF, Lim R, et al. FOXO1 couples metabolic activity and growth state in the vascular endothelium. Nature. 2016;529(7585):216-20. doi: 10.1038\/nature16498","DOI":"10.1038\/nature16498"},{"key":"ref50","doi-asserted-by":"publisher","unstructured":"51. Wang KC, Yeh YT, Nguyen P, Limqueco E, Lopez J, Thorossian S, et al. Flow-dependent YAP\/TAZ activities regulate endothelial phenotypes and atherosclerosis. Proc Natl Acad Sci U S A. 2016;113(41):11525-30. doi: 10.1073\/pnas.1613121113","DOI":"10.1073\/pnas.1613121113"},{"key":"ref51","doi-asserted-by":"publisher","unstructured":"52. Koo JH, Guan KL. Interplay between YAP\/TAZ and Metabolism. Cell Metab. 2018;28(2):196-206. doi: 10.1016\/j.cmet.2018.07.010","DOI":"10.1016\/j.cmet.2018.07.010"},{"key":"ref52","doi-asserted-by":"publisher","unstructured":"53. Zhang X, Zhao H, Li Y, Xia D, Yang L, Ma Y, et al. The role of YAP\/TAZ activity in cancer metabolic reprogramming. Mol Cancer. 2018;17(1):1-10. doi: 10.1186\/s12943-018-0882-1","DOI":"10.1186\/s12943-018-0882-1"},{"key":"ref53","doi-asserted-by":"publisher","unstructured":"54. Santinon G, Pocaterra A, Dupont S. Control of YAP\/TAZ Activity by Metabolic and Nutrient-Sensing Pathways. Trends Cell Biol. 2016;26(4):289-99. doi: 10.1016\/j.tcb.2015.11.004","DOI":"10.1016\/j.tcb.2015.11.004"},{"key":"ref54","doi-asserted-by":"publisher","unstructured":"55. Enzo E, Santinon G, Pocaterra A, Aragona M, Bresolin S, Forcato M, et al. Aerobic glycolysis tunes YAP\/TAZ transcriptional activity. EMBO J. 2015;34(10):1349-70. doi: 10.15252\/embj.201490379","DOI":"10.15252\/embj.201490379"},{"key":"ref55","doi-asserted-by":"publisher","unstructured":"56. Bertero T, Oldham WM, Cottrill KA, Pisano S, Vanderpool RR, Yu Q, et al. Vascular stiffness mechanoactivates YAP\/TAZ-dependent glutaminolysis to drive pulmonary hypertension. J Clin Invest. 2016;126(9):3313-35. doi: 10.1172\/JCI86387","DOI":"10.1172\/JCI86387"},{"key":"ref56","doi-asserted-by":"publisher","unstructured":"57. Kalucka J, Bierhansl L, Conchinha NV, Missiaen R, Elia I, Br\u00fcning U, et al. Quiescent Endothelial Cells Upregulate Fatty Acid \u03b2-Oxidation for Vasculoprotection via Redox Homeostasis. Cell Metab. 2018;28(6):881-94.e13. doi: 10.1016\/j.cmet.2018.07.016","DOI":"10.1016\/j.cmet.2018.07.016"},{"key":"ref57","doi-asserted-by":"publisher","unstructured":"58. Feinberg MW, Moore KJ. MicroRNA Regulation of Atherosclerosis. Circ Res. 2016;118(4):703-20. doi: 10.1161\/CIRCRESAHA.115.306300","DOI":"10.1161\/CIRCRESAHA.115.306300"},{"key":"ref58","doi-asserted-by":"publisher","unstructured":"59. Van Der Valk FM, Bekkering S, Kroon J, Yeang C, Van den Bossche J, van Buul JD, et al. Oxidized phospholipids on Lipoprotein(a) elicit arterial wall inflammation and an inflammatory monocyte response in humans. Circulation. 2016;134(8):611-24. doi: 10.1161\/CIRCULATIONAHA.116.020838","DOI":"10.1161\/CIRCULATIONAHA.116.020838"},{"key":"ref59","doi-asserted-by":"publisher","unstructured":"60. Chang MK, Binder CJ, Miller YI, Subbanagounder G, Silverman GJ, Berliner JA, et al. Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J Exp Med. 2004;200(11):1359-70. doi: 10.1084\/jem.20031763","DOI":"10.1084\/jem.20031763"},{"key":"ref60","doi-asserted-by":"publisher","unstructured":"61. Kuosmanen SM, Kansanen E, Kaikkonen MU, Sihvola V, Pulkkinen K, Jyrkk\u00e4nen H-K, et al. NRF2 regulates endothelial glycolysis and proliferation with MIR-93 and mediates the effects of oxidized phospholipids on endothelial activation. Nucleic Acids Res. 2018;46(3):1124-38. doi: 10.1093\/nar\/gkx1155","DOI":"10.1093\/nar\/gkx1155"},{"key":"ref61","doi-asserted-by":"publisher","unstructured":"62. Caruso P, Dunmore BJ, Schlosser K, Schoors S, Dos Santos C, Perez-Iratxeta C, et al. Identification of MicroRNA-124 as a Major Regulator of Enhanced Endothelial Cell Glycolysis in Pulmonary Arterial Hypertension via PTBP1 (Polypyrimidine Tract Binding Protein) and Pyruvate Kinase M2. Circulation. 2017;136(25):2451-67. doi: 10.1161\/CIRCULATIONAHA.117.028034","DOI":"10.1161\/CIRCULATIONAHA.117.028034"},{"key":"ref62","doi-asserted-by":"publisher","unstructured":"63. Fleg JL, Aronow WS, Frishman WH. Cardiovascular drug therapy in the elderly: Benefits and challenges. Nat Rev Cardiol. 2011;8(1):13-28. doi: 10.1038\/nrcardio.2010.162","DOI":"10.1038\/nrcardio.2010.162"},{"key":"ref63","doi-asserted-by":"publisher","unstructured":"64. Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, et al. Forecasting the future of cardiovascular disease in the United States: A policy statement from the American Heart Association. Circulation. 2011;123(8):933-44. doi: 10.1161\/CIR.0b013e31820a55f5","DOI":"10.1161\/CIR.0b013e31820a55f5"},{"key":"ref64","doi-asserted-by":"publisher","unstructured":"65. Sabbatinelli J, Prattichizzo F, Olivieri F, Procopio AD, Rippo MR, Giuliani A. Where Metabolism Meets Senescence: Focus on Endothelial Cells. Front Physiol. 2019;10:1523. doi: 10.3389\/fphys.2019.01523","DOI":"10.3389\/fphys.2019.01523"},{"key":"ref65","doi-asserted-by":"publisher","unstructured":"66. Tyrrell DJ, Blin MG, Song J, Wood SC, Zhang M, Beard DA, et al. Age-Associated Mitochondrial Dysfunction Accelerates Atherogenesis. Circ Res. 2020;126(3):298-314. doi: 10.1161\/CIRCRESAHA.119.315644","DOI":"10.1161\/CIRCRESAHA.119.315644"},{"key":"ref66","doi-asserted-by":"publisher","unstructured":"67. Rossman MJ, Gioscia-Ryan RA, Clayton ZS, Murphy MP, Seals DR. Targeting mitochondrial fitness as a strategy for healthy vascular aging. Clin Sci. 2020;134(12):1491-519. doi: 10.1042\/CS20190559","DOI":"10.1042\/CS20190559"},{"key":"ref67","doi-asserted-by":"publisher","unstructured":"68. Gioscia-Ryan RA, LaRocca TJ, Sindler AL, Zigler MC, Murphy MP, Seals DR. Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice. J Physiol. 2014;592(12):2549-61. doi: 10.1113\/jphysiol.2013.268680","DOI":"10.1113\/jphysiol.2013.268680"},{"key":"ref68","doi-asserted-by":"publisher","unstructured":"69. Rossman MJ, Santos-Parker JR, Steward CAC, Bispham NZ, Cuevas LM, Rosenberg HL, et al. Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults. Hypertens. 2018;71(6):1056-63. doi: 10.1161\/HYPERTENSIONAHA.117.10787","DOI":"10.1161\/HYPERTENSIONAHA.117.10787"},{"key":"ref69","doi-asserted-by":"publisher","unstructured":"70. Laina A, Stellos K, Stamatelopoulos K. Vascular ageing: Underlying mechanisms and clinical implications. Exp Gerontol. 2018;109:16-30. doi: 10.1016\/j.exger.2017.06.007","DOI":"10.1016\/j.exger.2017.06.007"},{"key":"ref70","doi-asserted-by":"publisher","unstructured":"71. Donato AJ, Machin DR, Lesniewski LA. Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease. Circ Res. 2018;123(7):825-48. doi: 10.1161\/CIRCRESAHA.118.312563","DOI":"10.1161\/CIRCRESAHA.118.312563"},{"key":"ref71","doi-asserted-by":"publisher","unstructured":"72. Palombo C, Kozakova M. Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications. Vascul Pharmacol. 2016;77:1-7. doi: 10.1016\/j.vph.2015.11.083","DOI":"10.1016\/j.vph.2015.11.083"},{"key":"ref72","doi-asserted-by":"publisher","unstructured":"73. Huynh J, Nishimura N, Rana K, Peloquin JM, Califano JP, Montague CR, et al. Age-related intimal stiffening enhances endothelial permeability and leukocyte transmigration. Sci Transl Med. 2011;3(112):112ra122. doi: 10.1126\/scitranslmed.3002761","DOI":"10.1126\/scitranslmed.3002761"},{"key":"ref73","doi-asserted-by":"publisher","unstructured":"74. Kohn JC, Zhou DW, Bordeleau F, Zhou AL, Mason BN, Mitchell MJ, et al. Cooperative effects of matrix stiffness and fluid shear stress on endothelial cell behavior. Biophys J. 2015;108(3):471-8. doi: 10.1016\/j.bpj.2014.12.023","DOI":"10.1016\/j.bpj.2014.12.023"},{"key":"ref74","doi-asserted-by":"publisher","unstructured":"75. Arts RJW, Novakovic B, ter Horst R, Carvalho A, Bekkering S, Lachmandas E, et al. Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. Cell Metab. 2016;24(6):807-19. doi: 10.1016\/j.cmet.2016.10.008","DOI":"10.1016\/j.cmet.2016.10.008"},{"key":"ref75","doi-asserted-by":"publisher","unstructured":"76. Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, et al. MTOR- and HIF-1\u03b1-mediated aerobic glycolysis as metabolic basis for trained immunity. Science. 2014;345(6204):1250684. doi: 10.1126\/science.1250684","DOI":"10.1126\/science.1250684"},{"key":"ref76","doi-asserted-by":"publisher","unstructured":"77. Bekkering S, Quintin J, Joosten LAB, Van Der Meer JWM, Netea MG, Riksen NP. Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arterioscler Thromb Vasc Biol. 2014;34(8):1731-8. doi: 10.1161\/ATVBAHA.114.303887","DOI":"10.1161\/ATVBAHA.114.303887"},{"key":"ref77","doi-asserted-by":"publisher","unstructured":"78. Keating ST, Groh L, Thiem K, Bekkering S, Li Y, Matzaraki V, et al. Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein. J Mol Med. 2020;98(6):819-31. doi: 10.1007\/s00109-020-01915-w","DOI":"10.1007\/s00109-020-01915-w"},{"key":"ref78","doi-asserted-by":"publisher","unstructured":"79. Que X, Hung M-Y, Yeang C, Gonen A, Prohaska TA, Sun X, et al. Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice. Nature. 2018;558(7709):301-6. doi: 10.1038\/s41586-018-0198-8","DOI":"10.1038\/s41586-018-0198-8"},{"key":"ref79","doi-asserted-by":"publisher","unstructured":"80. Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res. 2017;120(1):229-43. doi: 10.1161\/CIRCRESAHA.116.308537","DOI":"10.1161\/CIRCRESAHA.116.308537"},{"key":"ref80","doi-asserted-by":"publisher","unstructured":"81. Altun I, Oz F, Arkaya SC, Altun I, Bilge AK, Umman B, et al. Effect of statins on endothelial function in patients with acute coronary syndrome: a prospective study using adhesion molecules and flow-mediated dilatation. J Clin Med Res. 2014;6(5):354-61. doi: 10.14740\/jocmr1863w","DOI":"10.14740\/jocmr1863w"},{"key":"ref81","doi-asserted-by":"publisher","unstructured":"82. De Sotomayor M\u00c1, P\u00e9rez-Guerrero C, Herrrera MD, Jimenez L, Mar\u00edn R, Marhuenda E, et al. Improvement of age-related endothelial dysfunction by simvastatin: Effect on NO and COX pathways. Br J Pharmacol. 2005;146(8):1130-8. doi: 10.1038\/sj.bjp.0706420","DOI":"10.1038\/sj.bjp.0706420"},{"key":"ref82","doi-asserted-by":"publisher","unstructured":"83. Alvarez de Sotomayor M, P\u00e9rez-Guerrero C, Herrera MD, Marhuenda E. Effects of chronic treatment with simvastatin on endothelial dysfunction in spontaneously hypertensive rats. J Hypertens. 1999;17(6):769-76. doi: 10.1097\/00004872-199917060-00008","DOI":"10.1097\/00004872-199917060-00008"},{"key":"ref83","doi-asserted-by":"publisher","unstructured":"84. Kansui Y, Fujii K, Goto K, Abe I, Iida M. Effects of fluvastatin on endothelium-derived hyperpolarizing factor- and nitric oxide-mediated relaxations in arteries of hypertensive rats. Clin Exp Pharmacol Physiol. 2004;31(5-6):354-9. doi: 10.1111\/j.1440-1681.2004.04011.x","DOI":"10.1111\/j.1440-1681.2004.04011.x"},{"key":"ref84","doi-asserted-by":"publisher","unstructured":"85. Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97(12):1129-35. doi: 10.1161\/01.cir.97.12.1129","DOI":"10.1161\/01.CIR.97.12.1129"},{"key":"ref85","doi-asserted-by":"publisher","unstructured":"86. Sun W, Lee TS, Zhu M, Gu C, Wang Y, Zhu Y, et al. Statins activate AMP-activated protein kinase in vitro and in vivo. Circulation. 2006;114(24):2655-62. doi: 10.1161\/CIRCULATIONAHA.106.630194","DOI":"10.1161\/CIRCULATIONAHA.106.630194"},{"key":"ref86","doi-asserted-by":"publisher","unstructured":"87. Schoors S, De Bock K, Cantelmo AR, Georgiadou M, Ghesqui\u00e8re B, Cauwenberghs S, et al. Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis. Cell Metab. 2014;19(1):37-48. doi: 10.1016\/j.cmet.2013.11.008","DOI":"10.1016\/j.cmet.2013.11.008"},{"key":"ref87","doi-asserted-by":"publisher","unstructured":"88. Viney NJ, van Capelleveen JC, Geary RS, Xia S, Tami JA, Yu RZ, et al. Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials. Lancet. 2016;388(10057):2239-53. doi: 10.1016\/S0140-6736(16)31009-1","DOI":"10.1016\/S0140-6736(16)31009-1"},{"key":"ref88","doi-asserted-by":"publisher","unstructured":"89. Stiekema LCA, Prange KHM, Hoogeveen RM, Verweij SL, Kroon J, Schnitzler JG, et al. Potent lipoprotein(a) lowering following apolipoprotein(a) antisense treatment reduces the pro-inflammatory activation of circulating monocytes in patients with elevated lipoprotein(a). Eur Heart J. 2020 Jun 21;41(24):2262-71. doi: 10.1093\/eurheartj\/ehaa171","DOI":"10.1093\/eurheartj\/ehaa171"},{"key":"ref89","doi-asserted-by":"publisher","unstructured":"90. Medina-Leyte DJ, Dom\u00ednguez-P\u00e9rez M, Mercado I, Villarreal-Molina MT, Jacobo-Albavera L. Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review. Appl Sci. 2020;10(3):938. doi: 10.3390\/app10030938","DOI":"10.3390\/app10030938"},{"key":"ref90","doi-asserted-by":"publisher","unstructured":"91. Tan PH, Chan C, Xue SA, Dong R, Ananthesayanan B, Manunta M, et al. Phenotypic and functional differences between human saphenous vein (HSVEC) and umbilical vein (HUVEC) endothelial cells. Atherosclerosis. 2004;173(2):171-83. doi: 10.1016\/j.atherosclerosis.2003.12.011","DOI":"10.1016\/j.atherosclerosis.2003.12.011"},{"key":"ref91","doi-asserted-by":"publisher","unstructured":"92. Heiss M, Hellstr\u00f6m M, Kal\u00e9n M, May T, Weber H, Hecker M, et al. Endothelial cell spheroids as a versatile tool to study angiogenesis in vitro. FASEB J. 2015;29(7):3076-84. doi: 10.1096\/fj.14-267633","DOI":"10.1096\/fj.14-267633"},{"key":"ref92","doi-asserted-by":"publisher","unstructured":"93. Deli MA, \u00c1brah\u00e1m CS, Kataoka Y, Niwa M. Permeability studies on in vitro blood-brain barrier models: Physiology, pathology, and pharmacology. Cell Mol Neurobiol. 2005;25(1):59-127. doi: 10.1007\/s10571-004-1377-8","DOI":"10.1007\/s10571-004-1377-8"},{"key":"ref93","doi-asserted-by":"publisher","unstructured":"94. Donnini D, Perrella G, Stel G, Ambesi-Impiombato FS, Curcio F. A new model of human aortic endothelial cells in vitro. Biochimie. 2000;82(12):1107-14. doi: 10.1016\/S0300-9084(00)01195-0","DOI":"10.1016\/S0300-9084(00)01195-0"},{"key":"ref94","doi-asserted-by":"publisher","unstructured":"95. Cochrane A, Albers HJ, Passier R, Mummery CL, van den Berg A, Orlova VV, et al. Advanced in vitro models of vascular biology: Human induced pluripotent stem cells and organ-on-chip technology. Adv Drug Deliv Rev. 2019;140:68-77. doi: 10.1016\/j.addr.2018.06.007","DOI":"10.1016\/j.addr.2018.06.007"},{"key":"ref95","doi-asserted-by":"publisher","unstructured":"96. Nagy C, Haschemi A. Time and demand are two critical dimensions of immunometabolism: The process of macrophage activation and the pentose phosphate pathway. Front Immunol. 2015;6(APR):164. doi: 10.3389\/fimmu.2015.00164","DOI":"10.3389\/fimmu.2015.00164"},{"key":"ref96","doi-asserted-by":"publisher","unstructured":"97. Kim F, Tysseling KA, Rice J, Gallis B, Haji L, Giachelli CM, et al. Activation of IKK\u03b2 by glucose is necessary and sufficient to impair insulin signaling and nitric oxide production in endothelial cells. J Mol Cell Cardiol. 2005;39(2):327-34. doi: 10.1016\/j.yjmcc.2005.05.009","DOI":"10.1016\/j.yjmcc.2005.05.009"},{"key":"ref97","doi-asserted-by":"publisher","unstructured":"98. Du XL, Edelstein D, Dimmeler S, Ju Q, Sui C, Brownlee M. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. 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