{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T11:13:19Z","timestamp":1783681999816,"version":"3.55.0"},"reference-count":98,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Ischemia with non-obstructive coronary arteries (INOCA) and coronary microvascular dysfunction (CMD) are increasingly recognized causes of angina, reduced quality of life, and elevated cardiovascular risk, yet mechanistic heterogeneity complicates diagnosis and treatment. This narrative review synthesizes evidence from clinical guidelines, consensus documents, landmark trials, cohorts, mechanistic studies, and high-quality reviews identified through structured, non-exhaustive searches of PubMed\/MEDLINE, Google Scholar, and major cardiovascular society documents. Current evidence indicates that endothelial mitochondria function primarily as signaling organelles, regulating reactive oxygen species, nitric oxide bioavailability, endothelium-dependent hyperpolarization, calcium signaling, inflammatory activation, mitophagy, and endothelial survival. Cardiometabolic risk factors, aging, chronic kidney disease, and postmenopausal hormonal changes may converge on mitochondrial quality-control and redox pathways, contributing to CMD susceptibility and sex-specific vulnerability. However, direct human evidence linking endothelial mitochondrial dysfunction causally to CMD defined by invasive coronary function testing remains limited. Coronary physiological testing and acetylcholine provocation are validated tools for CMD endotyping, whereas mitochondrial biomarkers remain investigational. Endotype-guided diagnosis and management remain central, while mitochondria-targeted strategies require prospective CMD-specific validation.<\/jats:p>","DOI":"10.3390\/jcdd13070321","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:46:47Z","timestamp":1783676807000},"page":"321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial Mitochondrial Dysfunction in INOCA and Coronary Microvascular Dysfunction: Mechanisms, Sex Differences, and Therapeutic Implications"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3112-0656","authenticated-orcid":false,"given":"Roko","family":"Santic","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovre","family":"Martinovic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9696-3359","authenticated-orcid":false,"given":"Marko","family":"Kumric","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3452-389X","authenticated-orcid":false,"given":"Nikola","family":"Pavlovic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2060-5130","authenticated-orcid":false,"given":"Dinko","family":"Martinovic","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia"},{"name":"Department of Maxillofacial Surgery, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovre","family":"Jukic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-720X","authenticated-orcid":false,"given":"Zenon","family":"Pogorelic","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia"},{"name":"Department of Surgery, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-0635","authenticated-orcid":false,"given":"Josko","family":"Bozic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3415","DOI":"10.1093\/eurheartj\/ehae177","article-title":"2024 ESC Guidelines for the Management of Chronic Coronary Syndromes","volume":"45","author":"Vrints","year":"2024","journal-title":"Eur. 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