# Mechanisms of Coronary Microvascular Disease

> **NIH NIH K23** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $193,100

## Abstract

PROJECT SUMMARY:!
Each year millions of patients undergo cardiovascular evaluation for stable angina, which is typically caused by
flow-limiting stenosis of the epicardial coronary arteries. However, up to ~40% of men and ~60% of women
with stable angina referred for coronary angiography do not have obstructive coronary artery disease (CAD).
Even in patients with moderate to severe ischemia by stress testing, 21% have non-obstructive CAD, defined
as normal coronary arteries or <50% diameter stenosis in all epicardial coronary vessels at angiography. In the
absence of obstructive epicardial CAD, ischemia is often mediated by coronary microvascular disease.
Coronary microvascular disease is present in 25-40% of patients with ischemia and non-obstructive CAD and a
diagnosis of microvascular disease by invasive testing is associated with increased risks of death, myocardial
infarction, and heart failure. Non-invasive surrogate measures of coronary microvascular disease in non-
coronary vascular beds have not been identified.
Despite its prevalence and adverse clinical implications, the pathogenesis of coronary microvascular disease is
unknown. Coronary microvascular disease may reflect a systemic microvascular abnormality. Impairments in
microvascular function due to endothelial dysfunction, abnormal vasodilatory responses to stress, and
microvascular obstruction are hypothesized. Each of these processes may be in part mediated by platelet
interactions with the vascular endothelium. Activated platelets are known to induce endothelial dysfunction
directly and through interactions with inflammatory cells. Increased platelet aggregation has been reported in
stable patients with ischemia and non-obstructive CAD in comparison to both patients with obstructive CAD
and healthy controls. If platelets do mediate coronary microvascular disease, then modulation of platelet
activity could be therapeutic.
We propose to evaluate measures of platelet activity as a potential mechanism of coronary microvascular
disease in a cohort of men and women with stable ischemia and non-obstructive CAD undergoing invasive
measurements of microvascular function (Aim 1). We also plan to identify non-invasive correlates of coronary
microvascular disease in non-coronary microvascular beds that can be characterized in vivo (Aim 2). This may
facilitate diagnosis of microvascular disease in future clinical trials. This proposal will advance the training of
the PI as a clinical and translational investigator in ischemic heart disease through a curriculum of structured
mentorship, didactic coursework, participation in research-related conferences, and protected time for
research. The proposal addresses critical question 4.CQ.05 in NHLBI strategic visioning, will yield novel
insights into the physiology and mechanisms of coronary microvascular disease, and will provide a foundation
for future investigations into microvascular disease diagnosis, pathogenesis, and treatment.

## Key facts

- **NIH application ID:** 10228760
- **Project number:** 5K23HL150315-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Nathaniel Rosso Smilowitz
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $193,100
- **Award type:** 5
- **Project period:** 2020-08-04 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228760

## Citation

> US National Institutes of Health, RePORTER application 10228760, Mechanisms of Coronary Microvascular Disease (5K23HL150315-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10228760. Licensed CC0.

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