# Mechanisms of myelopoiesis after myocardial infarction

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $473,879

## Abstract

Project Summary/ Abstract:
An acute injury, such as myocardial infarction (MI), induces exaggerated production of myeloid cells in the
bone marrow. These newly generated myeloid cells are inflammatory and are crucial in disease
pathogenesis, exacerbating underlying processes such as atherosclerosis. However, the systemic long
distance signals and molecular mechanisms that trigger myelopoiesis in the bone marrow after an ischemic
event at a distant organ, such as the heart, are poorly understood. Our preliminary data revealed that,
following an MI, bone marrow hematopoietic stem and progenitor cells (HSPC) relocated into the vascular
niches. Vascular niches confer distinct microenvironments promoting HSPC proliferation and differentiation.
In investigating the long-distance signals produced after MI, we found increased levels of platelet-derived
extracellular vesicles (pEV) in the blood of patients and mice after MI. These pEV increased the expression
of PU.1, which is a myeloid transcription factor, and the receptor for interleukin-3 (IL-3R), which increases
myeloid cell generation, in bone marrow HSPC. Additionally, pEV isolated from mice with MI contained high
levels of miR-499, which increased bone marrow HSPC proliferation and differentiation in vitro. From these
observations, we hypothesize that increased miR-499 in pEV following MI relocates HSPC to active
vascular niches in the bone marrow, where they proliferate and differentiate into myeloid cells. We will test
this hypothesis in two specific aims: (1) We will determine the role of pEV in relocation of HSPC to the
vascular niches in the bone marrow. (2) We will investigate if increased miR-499 expression in pEV
augments myelopoiesis and atherosclerosis after MI. To test the hypothesis, we will photoconvert KikGR+
HSPC, use mice deficient of miR-499 and two different mouse models of atherosclerosis. We will
characterize pEV in patients and mice with MI using flow cytometry, ImageStream and NanoSight
technologies. Additionally, we will determine the proliferation of HSPC exposed to pEV isolated from miR-
499+/+ and miR-499-/- mice after MI in vitro and in vivo. The proposed grant application will further our
understanding of the mechanisms of MI-induced myelopoiesis, and explore new therapeutic avenues to
diminish inflammation and atherosclerosis after MI.

## Key facts

- **NIH application ID:** 10052051
- **Project number:** 1R01HL142629-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Partha Dutta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $473,879
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052051

## Citation

> US National Institutes of Health, RePORTER application 10052051, Mechanisms of myelopoiesis after myocardial infarction (1R01HL142629-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10052051. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*