Journal of cardiovascular development and diseaseJul 27, 2026

Blood Vessel Lining Mitochondria Problems in INOCA and Small Heart Vessel Dysfunction: Causes, Differences Between Men and Women, and Treatment Possibilities

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 3, 2026

Abstract

Ischemia with non-obstructive coronary arteries and coronary microvascular dysfunction may be linked to impaired mitochondrial function.

Endothelial mitochondria are involved in regulating several important cellular processes, including inflammation and calcium signaling.
Cardiometabolic risk factors and aging may influence mitochondrial quality-control pathways, potentially increasing susceptibility to coronary microvascular dysfunction.
Current evidence does not establish a direct causal relationship between mitochondrial dysfunction and coronary microvascular dysfunction in humans.
Validated tools like coronary physiological testing and acetylcholine provocation are used for diagnosing coronary microvascular dysfunction.
Mitochondrial biomarkers are still under investigation and not yet established for clinical use.

Simplified

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.

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Blood Vessel Lining Mitochondria Problems in INOCA and Small Heart Vessel Dysfunction: Causes, Differences Between Men and Women, and Treatment Possibilities

Abstract

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