The role of inflammation on coronary microvascular dysfunction and potential therapeutic targets.
6 affiliations
- 1Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, 4th Floor William Leech Building, Newcastle upon Tyne NE2 4HH, UK.
- 2Division of Cardiology, Department of Medicine, University of Verona, Verona 37129, Italy.
- 3The University of Adelaide, Adelaide 5005, Australia.
- 4Cedars-Sinai Medical Center, CA 90048, USA.
- 5Mount Sinai Medical Centre, New York, NY 10029, USA.
- 6Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE7 7DN, UK.
Abstract
Coronary microvascular dysfunction (CMD) is a major underlying cause of myocardial ischaemia and is associated with adverse cardiovascular outcomes. It occurs both in the presence of obstructive coronary artery disease (CAD) and in patients with non-obstructive CAD. Emerging evidence highlights chronic inflammation as a key factor in CMD pathogenesis. This review conceptualizes inflammation as a driver, amplifier, or consequence of CMD, depending on the underlying clinical phenotype. Pro-inflammatory pathways impair endothelial function and enhance immune cell infiltration within the coronary microcirculation, leading to myocardial ischaemia. Moreover, several chronic inflammatory conditions such as diabetes mellitus, obesity, and autoimmune diseases are linked with CMD. These conditions promote elevated circulating levels of pro-inflammatory cytokines, including high-sensitivity C-reactive protein, interleukins, tumour necrosis factor-α, and markers of monocyte activation. Inflammatory mechanisms of tissue damage-including adipose tissue inflammation, endothelial glycocalyx degradation, pericyte dysfunction, microvascular-specific immune cell infiltration, inflammasome signalling, microRNA dysregulation, and shear stress-induced inflammation-have been implicated in CMD. Recent advances in molecular and imaging biomarkers provide new opportunities for detecting and characterizing inflammation-driven CMD, although inflammation-specific diagnostic tools remain limited. While several therapies with anti-inflammatory or pleiotropic effects, including statins and sodium-glucose cotransporter-2 inhibitors, have demonstrated cardiovascular benefit, robust trials specifically evaluating coronary microvascular endpoints are scarce. This narrative review focuses on the chronic inflammatory mechanisms contributing to CMD, the available diagnostic techniques, and potential therapeutic strategies aimed at modulating inflammation to improve coronary microvascular function and cardiovascular outcomes.
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BibTeX
@article{wang2026role,
title = {{The role of inflammation on coronary microvascular dysfunction and potential therapeutic targets.}},
author = {Wanqi Wang and Martina Magistri and John Beltrame and Noel Bairey Merz and Roxana Mehran and Vijay Kunadian},
journal = {European heart journal open},
year = {2026},
month = sep,
doi = {10.1093/ehjopen/oeag153},
url = {https://europepmc.org/article/MED/42923701},
note = {CC BY},
}
RIS
TY - JOUR
TI - The role of inflammation on coronary microvascular dysfunction and potential therapeutic targets.
AU - Wanqi Wang
AU - Martina Magistri
AU - John Beltrame
AU - Noel Bairey Merz
AU - Roxana Mehran
AU - Vijay Kunadian
PY - 2026
DA - 2026/09/17
JO - European heart journal open
DO - 10.1093/ehjopen/oeag153
UR - https://europepmc.org/article/MED/42923701
AB - Coronary microvascular dysfunction (CMD) is a major underlying cause of myocardial ischaemia and is associated with adverse cardiovascular outcomes. It occurs both in the presence of obstructive coronary artery disease (CAD) and in patients with non-obstructive CAD. Emerging evidence highlights chronic inflammation as a key factor in CMD pathogenesis. This review conceptualizes inflammation as a driver, amplifier, or consequence of CMD, depending on the underlying clinical phenotype. Pro-inflammatory pathways impair endothelial function and enhance immune cell infiltration within the coronary microcirculation, leading to myocardial ischaemia. Moreover, several chronic inflammatory conditions such as diabetes mellitus, obesity, and autoimmune diseases are linked with CMD. These conditions promote elevated circulating levels of pro-inflammatory cytokines, including high-sensitivity C-reactive protein, interleukins, tumour necrosis factor-α, and markers of monocyte activation. Inflammatory mechanisms of tissue damage-including adipose tissue inflammation, endothelial glycocalyx degradation, pericyte dysfunction, microvascular-specific immune cell infiltration, inflammasome signalling, microRNA dysregulation, and shear stress-induced inflammation-have been implicated in CMD. Recent advances in molecular and imaging biomarkers provide new opportunities for detecting and characterizing inflammation-driven CMD, although inflammation-specific diagnostic tools remain limited. While several therapies with anti-inflammatory or pleiotropic effects, including statins and sodium-glucose cotransporter-2 inhibitors, have demonstrated cardiovascular benefit, robust trials specifically evaluating coronary microvascular endpoints are scarce. This narrative review focuses on the chronic inflammatory mechanisms contributing to CMD, the available diagnostic techniques, and potential therapeutic strategies aimed at modulating inflammation to improve coronary microvascular function and cardiovascular outcomes.
SN - 2752-4191
ER -