{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:09:39Z","timestamp":1789016979994,"version":"build-2803163510"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Aortic aneurysm and dissection (AAD) are life-threatening vascular diseases associated with progressive aortic wall degeneration and a high risk of rupture. Despite advances in surgical and endovascular techniques, effective disease-modifying pharmacological therapies remain limited. Mitochondria are central regulators of cellular energy metabolism, redox homeostasis, and apoptosis, and their functional integrity is essential for maintaining vascular homeostasis and aortic wall stability. Increasing evidence indicates that mitochondrial dysfunction plays a pivotal role in the initiation and progression of AAD. In this review, we summarize the major mechanisms by which mitochondrial abnormalities contribute to AAD pathogenesis, including impaired mitochondrial energy metabolism, defective mitochondrial biogenesis, excessive mitochondrial oxidative stress, and imbalanced mitochondrial dynamics. These interconnected processes promote vascular smooth muscle cell (VSMC) phenotypic switching, apoptosis, and senescence, alongside extracellular matrix degradation and inflammatory activation, ultimately culminating in the structural weakening of the aortic wall. We also discuss emerging mitochondria-targeted therapeutic strategies, including interventions aimed at restoring metabolic homeostasis, enhancing mitochondrial biogenesis, suppressing oxidative stress, and regulating mitochondrial fission-fusion balance. Although the clinical translation of these approaches remains hindered by inadequate target specificity and potential off-target effects, ameliorating mitochondrial dysfunction represents a promising strategy for developing non-surgical treatments for AAD. A deeper understanding of mitochondrial regulatory networks may provide new mechanistic insights and therapeutic opportunities for preventing AAD progression.<\/jats:p>","DOI":"10.3389\/fphar.2026.1942911","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:33:11Z","timestamp":1789014791000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial dysfunction in aortic aneurysm and dissection: mechanisms and therapeutic implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhili","family":"He","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug Targets and Translational Medicine for Cardio-cerebrovascular Diseases, Medical Basic Research Innovation Center for Cardiovascular and Cerebrovascular Diseases, Ministry of Education, School of Pharmacy, Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Song","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e220","DOI":"10.5114\/amsad\/210585","article-title":"Redox imbalance and oxidative stress in cardiovascular diseases: mechanisms, biomarkers, and therapeutic targets","volume":"10","author":"Ardahanl\u0131","year":"","journal-title":"Arch. 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