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Endothelial Mitochondrial Dysfunction in INOCA and Coronary Microvascular Dysfunction: Mechanisms, Sex Differences,

Roko Santic1,2, Lovre Martinovic1, Marko Kumric1,2

  • 1Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia.

Journal of Cardiovascular Development and Disease
|July 27, 2026
PubMed

Insights

Ischemia with non-obstructive coronary arteries (INOCA) and coronary microvascular dysfunction (CMD) are linked to mitochondrial dysfunction. While the connection is suspected, direct human evidence is limited, necessitating further research for targeted therapies.

Area of Science:

  • Cardiovascular Medicine
  • Mitochondrial Biology
  • Endothelial Function

Background:

  • Ischemia with non-obstructive coronary arteries (INOCA) and coronary microvascular dysfunction (CMD) are significant causes of angina and cardiovascular risk.
  • The underlying mechanisms are heterogeneous, complicating diagnosis and treatment strategies.

Purpose of the Study:

  • To review current evidence on the role of endothelial mitochondrial dysfunction in INOCA and CMD.
  • To explore potential links between cardiometabolic risk factors and mitochondrial pathways in CMD.

Main Methods:

  • A narrative review synthesizing evidence from clinical guidelines, trials, cohort studies, and mechanistic research.
  • Searches conducted in PubMed/MEDLINE, Google Scholar, and major cardiovascular society documents.

Main Results:

  • Endothelial mitochondria act as signaling organelles regulating key cellular processes.
  • Risk factors like aging and chronic kidney disease may impact mitochondrial function, contributing to CMD.
  • Direct human evidence causally linking mitochondrial dysfunction to CMD is currently limited.

Conclusions:

  • Endotype-guided diagnosis and management are crucial for INOCA and CMD.
  • Mitochondrial biomarkers for CMD are still investigational.
  • Mitochondria-targeted therapies require prospective validation in CMD patients.

Keywords:
INOCAcoronary function testingcoronary microvascular dysfunctionendothelial dysfunctionendothelial mitochondrial dysfunctionmitochondrial biomarkersmitochondrial reactive oxygen speciesmitophagynitric oxidesex differences

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