# Optimization of Antiplatelet Therapy to Target Platelet-Monocyte Aggregates in Myocardial Infarction

> **NIH VA I01** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2020 · —

## Abstract

Project Abstract/Summary
Despite advances in medical therapy and mechanical revascularization, myocardial infarction (MI)
remains a major cause of morbidity and mortality. While acute treatment of MI is associated with low
in-hospital mortality, a significant proportion of patients develop recurrent ischemic events during
long-term follow-up. Identifying inflammatory mechanisms underlying increased myocardial injury in
the peri-MI period may help direct novel therapeutics and more intensive medical therapy focused on
the etiology of disease. Recent evidence suggests that a specific monocyte subset (Mon2;
CD14++/CD16+) is a major pro-inflammatory mediator of cardiomyocyte injury during MI, but the
triggers leading to increased monocyte activation and recruitment are poorly defined. Platelets are
also a primary mediator of thrombotic injury: monocyte-platelet aggregates (MPA) are elevated in MI,
and the extent of their presence may be associated with the severity of tissue injury. These
observations have led to the formulation of the central hypothesis that MPA promote recruitment and
activation of pro-inflammatory monocytes during MI, and that appropriate anti-platelet drug therapy
can limit myocardial injury and long-term adverse cardiovascular events among patients with elevated
levels of MPA and monocyte activation. This project proposes to (1) quantitate the association between
circulating monocyte platelet aggregates (MPA) and cardiovascular outcomes after myocardial infarction, as
well as the circulating levels of CD14++CD16+ monocytes in myocardial infarction; (2investigate the monocyte
subtypes that are activated in MPA, the effect of inhibiting platelet P2Y12 receptors on MPA formation, and the
role of monocyte integrin activation in mediating monocyte adhesion; and (3) determine the differential
effect of antiplatelet agents on formation of MPA and monocyte activation. To test these hypotheses,
peripheral and coronary blood samples will be obtained at the time of cardiac catheterization and
percutaneous coronary intervention for treatment of MI. Blood samples will be analyzed by flow
cytometry to quantify MPA and monocyte subtypes. An arterial mimetic adhesion assay (A chip) will
be used to quantitate monocyte subset adhesion to VCAM-1, and the relative adhesion of monocyte
subtypes in MPA. Clinical follow-up will establish a relationship between MPA, monocyte subset
activation, and major adverse cardiovascular events. In vitro and clinical analysis of the effect of more
intensive platelet inhibition with ticagrelor or prasugrel on MPA will identify future therapeutic
strategies for individualized antiplatelet treatment among patients after MI.

## Key facts

- **NIH application ID:** 9979786
- **Project number:** 5I01CX001458-04
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** EHRIN J ARMSTRONG
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979786

## Citation

> US National Institutes of Health, RePORTER application 9979786, Optimization of Antiplatelet Therapy to Target Platelet-Monocyte Aggregates in Myocardial Infarction (5I01CX001458-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979786. Licensed CC0.

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