# Studies on the effects of colchicine on neutrophil biology in acute myocardial infarction

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $420,371

## Abstract

Patient with ST-segment elevation myocardial infarction (STEMI) have a high risk of recurrent major adverse
cardiovascular events (MACE) (approximately 20% at three years). Vascular inflammation plays a key role in
this pathogenesis of recurrent MACE, and neutrophils are the most abundant of inflammatory cells. Neutrophils
adhere to inflamed or injured endothelium, migrate into the vessel wall, release proteolytic enzymes that can
lead to erosion or rupture of plaque, and activate the inflammasome and synthesis of interleukin-1β, a known
target for therapy for secondary prevention of cardiovascular events. Neutrophils also release neutrophil
extracellular traps (NETs) and microparticles, both of which may promote sustained inflammatory signaling and
thrombus generation even after neutrophil death.
Colchicine is a safe, well-tolerated anti-inflammatory agent that preferentially accumulates in neutrophils
compared with other inflammatory cells. Colchicine inhibits chemotaxis, endothelial adhesion, and
extravasation of neutrophils at sites of endothelial injury or inflammation; suppresses the inflammasome-
mediated production of interleukin-1β; and reduces inflammation and MACE in patients with stable heart
disease. The effects of colchicine in patients with STEMI, however, is not known. The CLEAR SYNERGY
study is a multicenter randomized trial of colchicine versus placebo in 4000 STEMI patients treated with PCI.
This proposal leverages the CLEAR SYNERGY study to obtain blood samples for neutrophil characterization.
The aims of this proposal are to 1) assess the effect of colchicine on neutrophil activation, including neutrophil-
driven responses such as NETs and microparticles, 2) examine the clinical and genetic factors that may
determine heterogeneity of treatment response based on neutrophil activity markers, and 3) develop a risk
score based on markers of neutrophil activity to predict occurrence of MACE over 3 years after STEMI, and
assess the impact of colchicine on the relation between this risk score and MACE. By utilizing blood specimens
derived from CLEAR SYNERGY study participants immediately after STEMI and on 3-month follow-up, this
proposal offers the opportunity to provide mechanistic insight into the findings of this large randomized trial;
cost-effectively add scientific value independent of the CLEAR SYNTERGY study findings; potentially promote
discovery of novel selective targets and therapeutic options to reduce cardiovascular inflammation with minimal
immunosuppression; and foster a personalized medicine approach to therapy after STEMI. Finally, findings
from this study may also open a door to novel therapeutic strategies in other settings of cardiovascular
inflammation and injury (e.g., peripheral artery disease, stroke) and other disease states in which neutrophils
play a pivotal role (e.g., vasculitis, wound healing).

## Key facts

- **NIH application ID:** 10104529
- **Project number:** 5R01HL146206-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Binita Shah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $420,371
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104529

## Citation

> US National Institutes of Health, RePORTER application 10104529, Studies on the effects of colchicine on neutrophil biology in acute myocardial infarction (5R01HL146206-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10104529. Licensed CC0.

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