{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:37:28Z","timestamp":1762522648246,"version":"build-2065373602"},"reference-count":119,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["20-45-08002"],"award-info":[{"award-number":["20-45-08002"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Thoracic aortic aneurysm (TAA) is a life-threatening condition associated with high mortality, in which the aortic wall is deformed due to congenital or age-associated pathological changes. The mechanisms of TAA development remain to be studied in detail, and are the subject of active research. In this review, we describe the morphological changes of the aortic wall in TAA. We outline the genetic disorders associated with aortic enlargement and discuss the potential role of mitochondrial pathology, in particular mitochondrial DNA heteroplasmy, in the disease pathogenesis.<\/jats:p>","DOI":"10.3390\/life11121395","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T01:20:41Z","timestamp":1639444841000},"page":"1395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular Pathogenesis and the Possible Role of Mitochondrial Heteroplasmy in Thoracic Aortic Aneurysm"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0613-8556","authenticated-orcid":false,"given":"A. V.","family":"Suslov","sequence":"first","affiliation":[{"name":"National Medical Research Center of Cardiology, Moscow 121552, Russia"},{"name":"Department of Human Anatomy, First Moscow State Medical University (Sechenov University), Moscow 119435, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. A.","family":"Afanasyev","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Moscow 121552, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. A.","family":"Degtyarev","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, First Moscow State Medical University (Sechenov University), Moscow 119435, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. V.","family":"Chumachenko","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Moscow 121552, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Bagheri","family":"Ekta","sequence":"additional","affiliation":[{"name":"Research Institute of Human Morphology, Moscow 117418, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0312-3773","authenticated-orcid":false,"given":"V. N.","family":"Sukhorukov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Moscow 121552, Russia"},{"name":"Research Institute of Human Morphology, Moscow 117418, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2096-3237","authenticated-orcid":false,"given":"V. A.","family":"Khotina","sequence":"additional","affiliation":[{"name":"Research Institute of Human Morphology, Moscow 117418, Russia"},{"name":"Institute of General Pathology and Pathophysiology, Moscow 125315, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9097-3962","authenticated-orcid":false,"given":"S.-F.","family":"Yet","sequence":"additional","affiliation":[{"name":"Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan Town 35053, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0978-6444","authenticated-orcid":false,"given":"I. A.","family":"Sobenin","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Moscow 121552, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Yu","family":"Postnov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Moscow 121552, Russia"},{"name":"Research Institute of Human Morphology, Moscow 117418, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1161\/hc4901.100362","article-title":"Staged Repair of Extensive Aortic Aneurysms","volume":"104","author":"Safi","year":"2001","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1097\/01.pas.0000213270.38091.69","article-title":"Surgical pathology of the ascending aorta: A clinicopathologic study of 513 cases","volume":"30","author":"Homme","year":"2006","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"ITC5-1","DOI":"10.7326\/0003-4819-150-9-200905050-01005","article-title":"In the clinic. Abdominal aortic aneurysm","volume":"150","author":"Lederle","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1378\/chest.122.1.311","article-title":"Clinical, diagnostic, and management perspectives of aortic dissection","volume":"122","author":"Khan","year":"2002","journal-title":"Chest"},{"key":"ref_5","first-page":"505","article-title":"Surgical pathology of chronic ascending aortic dissections","volume":"40","author":"Vaideeswar","year":"2008","journal-title":"Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1097\/01.pas.0000213293.04026.ec","article-title":"Surgical pathology of noninfectious ascending aortitis: A study of 45 cases with emphasis on an isolated variant","volume":"30","author":"Miller","year":"2006","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0002-9149(77)80005-2","article-title":"Pathogenesis of dissecting aneurysm of aorta: Comparative histopathologic study of significance of medial changes","volume":"39","author":"Schlatmann","year":"1977","journal-title":"Am. J. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Meyer, W.W., Walsh, S.Z., and Lind, J. (1980). Functional Morphology of Human Arteries during Fetal and Postnatal Develop-Ment. Structure and Function of the Circulation, Springer.","DOI":"10.1007\/978-1-4615-7924-3_3"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1159\/000331278","article-title":"Age-Related Changes in the Elastic Tissue of the Human Aorta","volume":"49","author":"Fritze","year":"2012","journal-title":"J. Vasc. Res."},{"key":"ref_10","first-page":"1119","article-title":"Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Comparison between occidental and Chinese communities","volume":"139","author":"Virmani","year":"1991","journal-title":"Am. J. Pathol."},{"key":"ref_11","first-page":"1103","article-title":"Thoracic aortic aneurysms: A population-Based study","volume":"92","author":"Bickerstaff","year":"1982","journal-title":"Surgery"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"441","DOI":"10.7326\/0003-4819-126-6-199703150-00004","article-title":"Prevalence and associations of ab-dominal aortic aneurysm detected through screening. Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Group","volume":"126","author":"Lederle","year":"1997","journal-title":"Ann. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1097\/00132586-199908000-00011","article-title":"Improved Prognosis of Thoracic Aortic Aneurysms: A Population-Based Study","volume":"43","author":"Clouse","year":"1999","journal-title":"Surv. Anesthesiol."},{"key":"ref_14","first-page":"717","article-title":"Medionecrosis Aortae Idiopathica Cystica*","volume":"8","author":"Moritz","year":"1932","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1016\/0046-8177(93)90267-K","article-title":"New observations on the etiology of aortic valve disease: A surgical pathologic study of 236 cases from 1990","volume":"24","author":"Dare","year":"1993","journal-title":"Hum. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0003-4975(10)61842-5","article-title":"Ruptured aneurysms of the sinus of Valsalva","volume":"42","author":"Mayer","year":"1986","journal-title":"Ann. Thorac. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"W495","DOI":"10.2214\/AJR.09.3570","article-title":"Sinus of Valsalva Aneurysms: Assessment with Cardiovascular MRI","volume":"194","author":"Hoey","year":"2010","journal-title":"Am. J. Roentgenol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0003-4975(99)01291-6","article-title":"Thoracic aortic aneurysms: Treatment with endovascular self-Expandable stent grafts","volume":"69","author":"Hutschala","year":"2000","journal-title":"Ann. Thorac. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/cge.12436","article-title":"Cardiovascular manifestations in Marfan syndrome and related diseases; multiple genes causing similar phenotypes","volume":"87","author":"Cook","year":"2015","journal-title":"Clin. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1126\/science.1124287","article-title":"Losartan, an AT1 Antagonist, Prevents Aortic Aneurysm in a Mouse Model of Marfan Syndrome","volume":"312","author":"Habashi","year":"2006","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ng1116","article-title":"Dysregulation of TGF-beta activation con-tributes to pathogenesis in Marfan syndrome","volume":"33","author":"Neptune","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1172\/JCI200422715","article-title":"TGF-Beta-Dependent pathogenesis of mitral valve pro-Lapse in a mouse model of Marfan syndrome","volume":"114","author":"Ng","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1097\/HCO.0000000000000114","article-title":"Familial thoracic aortic aneurysms","volume":"29","author":"Jondeau","year":"2014","journal-title":"Curr Opin Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S0733-8651(05)70181-8","article-title":"Aortic dissection","volume":"18","author":"Flachskampf","year":"2000","journal-title":"Cardiol. Clin."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1001\/jama.283.7.897","article-title":"The International Registry of Acute Aortic Dissection (IRAD): New insights into an old disease","volume":"283","author":"Hagan","year":"2000","journal-title":"JAMA"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Parakatselaki, M.-E., and Ladoukakis, E. (2021). mtDNA Heteroplasmy: Origin, Detection, Significance, and Evolutionary Consequences. Life, 11.","DOI":"10.3390\/life11070633"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1073\/pnas.1419651112","article-title":"Extensive tissue-related and allele-related mtDNA heteroplasmy suggests positive selection for somatic mutations","volume":"112","author":"Li","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1101\/gr.203216.115","article-title":"Transmission of human mtDNA heteroplasmy in the Genome of the Netherlands families: Support for a variable-size bottleneck","volume":"26","author":"Li","year":"2016","journal-title":"Genome Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kaarniranta, K., Pawlowska, E., Szczepa\u0144ska, J., Jablkowska, A., and Blasiak, J. (2019). Role of Mitochondrial DNA Damage in ROS-Mediated Pathogenesis of Age-Related Macular Degeneration (AMD). Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102374"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11244","DOI":"10.1093\/nar\/gkaa804","article-title":"Mechanisms of replication and repair in mitochondrial DNA deletion formation","volume":"48","author":"Fontana","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"671908","DOI":"10.3389\/fmolb.2021.671908","article-title":"The Role of Mitochondrial Dysfunction in Vascular Disease, Tumorigenesis, and Diabetes","volume":"8","author":"Zhunina","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nrg3966","article-title":"The dynamics of mitochondrial DNA heteroplasmy: Implications for human health and disease","volume":"16","author":"Stewart","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"762","DOI":"10.3389\/fgene.2020.00762","article-title":"Evidence of Selection Against Damaged Mitochondria During Early Embryogenesis in the Mouse","volume":"11","author":"Machado","year":"2020","journal-title":"Front. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1042\/bj20021594","article-title":"Mitochondrial threshold effects","volume":"370","author":"Rossignol","year":"2003","journal-title":"Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41576-020-00284-x","article-title":"Extreme heterogeneity of human mitochondrial DNA from organelles to populations","volume":"22","author":"Stewart","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/nrg3275","article-title":"Human mitochondrial DNA: Roles of inherited and somatic mutations","volume":"13","author":"Schon","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-physiol-020518-114358","article-title":"Evolving Concepts of Mitochondrial Dynamics","volume":"81","author":"Dorn","year":"2019","journal-title":"Annu. Rev. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1038\/s41467-017-01919-0","article-title":"Mitochondrial dynamics controls anti-Tumour innate immunity by regulating CHIP-IRF1 axis stability","volume":"8","author":"Gao","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cell.2016.05.035","article-title":"Mitochondrial Dynamics Controls T Cell Fate through Metabolic Programming","volume":"166","author":"Buck","year":"2016","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101255","DOI":"10.1016\/j.redox.2019.101255","article-title":"Mitochondria as central hub of the immune system","volume":"26","author":"Davanzo","year":"2019","journal-title":"Redox. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.bbamem.2011.10.025","article-title":"The role of VDAC in cell death: Friend or foe?","volume":"1818","author":"McCommis","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.cell.2005.08.012","article-title":"Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-KappaB and IRF 3","volume":"122","author":"Seth","year":"2005","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1242\/jcs.115.8.1663","article-title":"Membrane topology and mitochondrial targeting of mitofusins, ubiq-uitous mam-Malian homologs of the transmembrane GTPase Fzo","volume":"115","author":"Rojo","year":"2002","journal-title":"J. Cell. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1083\/jcb.152.4.683","article-title":"Connection of the Mitochondrial Outer and Inner Membranes by Fzo1 Is Critical for Organellar Fusion","volume":"152","author":"Fritz","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/ncb1206-1317","article-title":"Upgrading the BCL-2 network","volume":"8","author":"Galonek","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1126\/science.1138870","article-title":"Cell biology. Cellular Demolition and the Rules of Engagement","volume":"315","author":"Youle","year":"2007","journal-title":"Science"},{"key":"ref_47","first-page":"1418","article-title":"Mitochondrial matrix processes","volume":"80","author":"Mazunin","year":"2015","journal-title":"Biochemistry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nri.2016.58","article-title":"Inflammasomes: Mechanism of assembly, regulation and signalling","volume":"16","author":"Broz","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.immuni.2013.08.001","article-title":"Mitochondrial Cardiolipin Is Required for Nlrp3 Inflammasome Activation","volume":"39","author":"Iyer","year":"2013","journal-title":"Immunity"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Orekhov, A.N., Nikiforov, N.N., Ivanova, E.A., and Sobenin, I.A. (2020). Possible Role of Mitochondrial DNA Mutations in Chronification of Inflammation: Focus on Atherosclerosis. J. Clin. Med., 9.","DOI":"10.3390\/jcm9040978"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kim, Y.G., Kim, S.-M., Kim, K.-P., Lee, S.-H., and Moon, J.-Y. (2019). The Role of Inflammasome-Dependent and Inflam-masome-Independent NLRP3 in the Kidney. Cells, 8.","DOI":"10.3390\/cells8111389"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bcp.2019.03.008","article-title":"Role of mitochondrial dysfunction on rheumatic diseases","volume":"165","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1161\/ATVBAHA.116.307648","article-title":"NLRP3 (Nucleotide Oligomerization Domain\u2013Like Receptor Family, Pyrin Domain Containing 3)\u2013Caspase-1 Inflammasome Degrades Contractile Proteins","volume":"37","author":"Wu","year":"2017","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","article-title":"Mitochondrial diseases","volume":"2","author":"Gorman","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.yexmp.2006.09.008","article-title":"Mitochondrial dysfunction and molecular pathways of disease","volume":"83","author":"Pieczenik","year":"2007","journal-title":"Exp. Mol. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bbadis.2016.11.010","article-title":"Mitochondrial dysfunction and oxidative stress in metabolic disorders\u2014A step towards mitochondria based therapeutic strategies","volume":"1863","author":"Bhatti","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0355-7","article-title":"Mitochondrial dysfunction and oxidative stress in heart disease","volume":"51","author":"Peoples","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e002555","DOI":"10.1161\/JAHA.115.002555","article-title":"Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet-Induced Metabolic Heart Disease","volume":"5","author":"Sverdlov","year":"2016","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1084\/jem.20102049","article-title":"Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS)","volume":"208","author":"Bulua","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev.immunol.021908.132715","article-title":"The Inflammasomes: Guardians of the Body","volume":"27","author":"Martinon","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/ni.1831","article-title":"Thioredoxin-interacting protein links oxidative stress to inflammasome activation","volume":"11","author":"Zhou","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive Oxygen Species in Inflammation and Tissue Injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mito.2017.12.001","article-title":"Mitochondrial dysfunction and damage associated molecular patterns (DAMPs) in chronic in-flammatory diseases","volume":"41","author":"Kang","year":"2018","journal-title":"Mitochondrion"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Picca, A., Lezza, A.M.S., Leeuwenburgh, C., Pesce, V., Calvani, R., and Landi, F. (2017). Fueling Inflamm-Aging through Mi-tochondrial Dysfunction: Mechanisms and Molecular Targets. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050933"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4050796","DOI":"10.1155\/2019\/4050796","article-title":"The Role of Mitochondrial Damage-Associated Molecular Patterns in Chronic Neuroin-flammation","volume":"2019","author":"Bajwa","year":"2019","journal-title":"Mediators Inflamm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1161\/CIRCULATIONAHA.106.646091","article-title":"Critical Role of Monocyte Chemoattractant Protein-1\/CC Chemokine Ligand 2 in the Pathogenesis of Ischemic Cardiomyopathy","volume":"115","author":"Frangogiannis","year":"2007","journal-title":"Circulation"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.jhep.2017.02.026","article-title":"Targeting hepatic macrophages to treat liver diseases","volume":"66","author":"Tacke","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.addr.2017.12.019","article-title":"Targeting renal fibrosis: Mechanisms and drug delivery systems","volume":"129","author":"Nastase","year":"2018","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1074-7613(00)80165-X","article-title":"Chemokines: A New Classification System and Their Role in Immunity","volume":"12","author":"Zlotnik","year":"2000","journal-title":"Immun"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zhang, X., Yun, J.S., Han, D., Yook, J.I., Kim, H.S., and Cho, E.S. (2020). TGF-\u03b2 Pathway in Salivary Gland Fibrosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239138"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Arias, M., Sauer-Lehnen, S., Treptau, J., Janoschek, N., Theuerkauf, I., Buettner, R., Gressner, A.M., and Weiskirchen, R. (2003). Adenoviral expression of a transforming growth factor-beta1 antisense mRNA is effective in preventing liver fibrosis in bile-duct ligated rats. BMC Gastroenterol., 3.","DOI":"10.1186\/1471-230X-3-29"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00018-013-1349-6","article-title":"The pathogenesis of cardiac fibrosis","volume":"71","author":"Kong","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.mam.2018.07.001","article-title":"Cardiac fibrosis: Cell biological mechanisms, molecular pathways and therapeutic opportu-nities","volume":"65","author":"Frangogiannis","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4254\/wjh.v10.i1.1","article-title":"Role of inflammatory response in liver diseases: Therapeutic strategies","volume":"10","author":"Gallego","year":"2018","journal-title":"World J. Hepatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1007\/s10753-018-0742-6","article-title":"IL-33 Can Promote the Process of Pulmonary Fibrosis by Inducing the Imbalance Between MMP-9 and TIMP-Inflammation","volume":"41","author":"Wu","year":"2018","journal-title":"Inflammation."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.yjmcc.2019.01.018","article-title":"Dysregulation of IL-33\/ST2 signaling and myocardial periarteriolar fibrosis","volume":"128","author":"Garbern","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.redox.2015.08.015","article-title":"Redox-fibrosis: Impact of TGF\u03b21 on ROS generators, mediators and functional consequences","volume":"6","author":"Richter","year":"2015","journal-title":"Redox Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00441-016-2445-3","article-title":"Reactive oxygen species and fibrosis: Further evidence of a significant liaison","volume":"365","author":"Richter","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.redox.2015.06.012","article-title":"Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms","volume":"5","author":"Manea","year":"2015","journal-title":"Redox Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1038\/ki.2014.386","article-title":"p47phox contributes to albuminuria and kidney fibrosis in mice","volume":"87","author":"Wang","year":"2015","journal-title":"Kidney Int."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Murphy-Marshman, H., Quensel, K., Shi-Wen, X., Barnfield, R., Kelly, J., Peidl, A., Stratton, R.J., and Leask, A. (2017). Antioxidants and NOX1\/NOX4 inhibition blocks TGF\u03b21-induced CCN2 and \u03b1-SMA expression in dermal and gingival fibroblasts. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0186740"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1080\/13510002.2021.1899473","article-title":"Oxidative stress in genetically triggered thoracic aortic aneurysm: Role in pathogenesis and therapeutic opportunities","volume":"26","author":"Portelli","year":"2021","journal-title":"Redox Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5392454","DOI":"10.1155\/2020\/5392454","article-title":"Oxidant\/Antioxidant Profile in the Thoracic Aneurysm of Patients with the Loeys-Dietz Syndrome","volume":"2020","author":"Soto","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fphar.2014.00123","article-title":"Fibroblasts in fibrosis: Novel roles and mediators","volume":"5","author":"Kendall","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/BF03403533","article-title":"Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair","volume":"1","author":"Bucala","year":"1994","journal-title":"Mol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.biocel.2003.10.005","article-title":"Circulating fibrocytes: Collagen-secreting cells of the peripheral blood","volume":"36","author":"Quan","year":"2004","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mam.2018.06.003","article-title":"Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications","volume":"65","author":"Weiskirchen","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1242\/jcs.103.2.521","article-title":"Transforming growth factor beta 1 promotes the differentiation of endothelial cells into smooth muscle-like cells in vitro","volume":"103","author":"Arciniegas","year":"1992","journal-title":"J. Cell Sci."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Piera-Velazquez, S., Mendoza, F.A., and Jimenez, S.A. (2016). Endothelial to Mesenchymal Transition (EndoMT) in the Patho-Genesis of Human Fibrotic Diseases. J. Clin. Med., 5.","DOI":"10.3390\/jcm5040045"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5577634","DOI":"10.1155\/2021\/5577634","article-title":"Endothelial Cell-Derived SO2 Controls Endothelial Cell Inflammation, Smooth Muscle Cell Proliferation, and Collagen Synthesis to Inhibit Hypoxic Pulmonary Vascular Remodelling","volume":"2021","author":"Liu","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e139445","DOI":"10.1172\/jci.insight.139445","article-title":"Smooth muscle\u2013derived progenitor cell myofibroblast differentiation through KLF4 downregulation promotes arterial remodeling and fibrosis","volume":"5","author":"Lu","year":"2020","journal-title":"JCI Insight"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"H2829-37","DOI":"10.1152\/ajpheart.2000.279.6.H2829","article-title":"Mechanisms by which bradykinin promotes fibrosis in vascular smooth muscle cells: Role of TGF-Beta and MAPK","volume":"279","author":"Douillet","year":"2000","journal-title":"Am. J. Physiol. Heart. Circ. Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"jcs227900","DOI":"10.1242\/jcs.227900","article-title":"The myofibroblast at a glance","volume":"133","author":"Pakshir","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-56955-1","article-title":"Transcriptomic changes during TGF-\u03b2-mediated differentiation of airway fibroblasts to myofibroblasts","volume":"9","author":"Walker","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"20377","DOI":"10.1111\/imr.12619","article-title":"Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family","volume":"281","author":"Cayrol","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.matbio.2017.11.010","article-title":"Inflammation and fibrosis","volume":"68\u201369","author":"Mack","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"6443","DOI":"10.1007\/s11033-021-06646-w","article-title":"M2-polarized macrophages mediate wound healing by regulating connective tissue growth factor via AKT, ERK1\/2, and STAT3 signaling pathways","volume":"48","author":"Zhang","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"M\u00e9ndez-Barbero, N., Guti\u00e9rrez-Mu\u00f1oz, C., and Blanco-Colio, L.M. (2021). Cellular Crosstalk between Endothelial and Smooth Muscle Cells in Vascular Wall Remodeling. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147284"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1161\/01.ATV.0000214999.12921.4f","article-title":"Inflammation and Cellular Immune Responses in Abdominal Aortic Aneurysms","volume":"26","author":"Shimizu","year":"2006","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Infantes, D., Nus, M., Navas-Madro\u00f1al, M., Fit\u00e9, J., P\u00e9rez, B., Barros-Membrilla, A., Soto, B., Mart\u00ednez-Gonz\u00e1lez, J., Camacho, M., and Rodriguez, C. (2021). Oxidative Stress and Inflammatory Markers in Abdominal Aortic Aneurysm. Antioxidants, 10.","DOI":"10.3390\/antiox10040602"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.2174\/1381612827666210210142200","article-title":"Thoracic Aortic Aneurysm: Blood Pressure and Inflammation as Key Factors in the Development of Aneurysm Dissection","volume":"27","author":"Postnov","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"a029827","DOI":"10.1101\/cshperspect.a029827","article-title":"Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise","volume":"8","author":"Safdar","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"25700","DOI":"10.18632\/oncotarget.14878","article-title":"Emerging role of exosome-mediated intercellular communication in vascular remodeling","volume":"8","author":"Su","year":"2017","journal-title":"Oncotarget"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"545","DOI":"10.5551\/jat.51102","article-title":"Exosome-Derived MiRNAs as Biomarkers of the Development and Progression of Intracranial Aneurysms","volume":"27","author":"Liao","year":"2020","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e010332","DOI":"10.1161\/JAHA.118.010332","article-title":"Elevated Wall Tension Leads to Reduced miR-133a in the Thoracic Aorta by Exosome Release","volume":"8","author":"Akerman","year":"2019","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.athoracsur.2020.03.017","article-title":"Shear Stress and Aortic Strain Associations with Biomarkers of Ascending Thoracic Aortic Aneurysm","volume":"110","author":"Pasta","year":"2020","journal-title":"Ann. Thorac. Surg."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/jth.13608","article-title":"Association of ficolin-3 with abdominal aortic aneurysm presence and progression","volume":"15","author":"Burillo","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1161\/ATVBAHA.116.303229","article-title":"Altered Smooth Muscle Cell Force Generation as a Driver of Thoracic Aortic Aneurysms and Dissections","volume":"37","author":"Milewicz","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Kulek, A.R., Anzell, A., Wider, J.M., Sanderson, T.H., and Przyklenk, K. (2020). Mitochondrial Quality Control: Role in Cardiac Models of Lethal Ischemia-Reperfusion Injury. Cells, 9.","DOI":"10.3390\/cells9010214"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1089\/ars.2015.6294","article-title":"The Mitochondria in Diabetic Heart Failure: From Pathogenesis to Therapeutic Promise","volume":"22","author":"Schilling","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"689101","DOI":"10.3389\/fcvm.2021.689101","article-title":"Mitochondrial Arrest on the Microtubule Highway\u2014A Feature of Heart Failure and Diabetic Cardiomyopathy?","volume":"8","author":"Kassab","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11906-017-0710-9","article-title":"Role of Mitochondrial Dysfunction in Hypertension and Obesity","volume":"19","author":"Lahera","year":"2017","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-0716-1266-8_1","article-title":"Mitochondrial Dysfunction in Mitochondrial Medicine: Current Limitations, Pitfalls, and Tomorrow","volume":"2276","author":"Gueguen","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"116927","DOI":"10.1016\/j.lfs.2019.116927","article-title":"Targeted depletion of monocyte\/macrophage suppresses aortic dissection with the spatial regulation of MMP-9 in the aorta","volume":"254","author":"Li","year":"2020","journal-title":"Life Sci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jtcvs.2005.09.018","article-title":"Characterization of the inflammatory and apoptotic cells in the aortas of patients with ascending thoracic aortic aneurysms and dissections","volume":"131","author":"He","year":"2006","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Creamer, T.J., Bramel, E.E., and MacFarlane, E.G. (2021). Insights on the Pathogenesis of Aneurysm through the Study of Hered-itary Aortopathies. Genes, 12.","DOI":"10.3390\/genes12020183"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1161\/01.RES.88.1.37","article-title":"Phenotypic Alteration of Vascular Smooth Muscle Cells Precedes Elastolysis in a Mouse Model of Marfan Syndrome","volume":"88","author":"Bunton","year":"2001","journal-title":"Circ. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1093\/cvr\/cvy180","article-title":"Mitochondrial function in thoracic aortic aneurysms","volume":"114","author":"Yu","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"529075","DOI":"10.3389\/fphys.2020.529075","article-title":"The Dynamic Interplay between Cardiac Inflammation and Fibrosis","volume":"11","author":"Thomas","year":"2020","journal-title":"Front. Physiol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/12\/1395\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:46:30Z","timestamp":1760168790000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/12\/1395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,13]]},"references-count":119,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["life11121395"],"URL":"https:\/\/doi.org\/10.3390\/life11121395","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2021,12,13]]}}}