# Project 3:  Remote control of hematopoiesis in cardiovascular disease

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $399,886

## Abstract

Atherosclerosis, the underlying cause of myocardial infarction and stroke, is a lipid-driven
chronic inflammatory disease characterized by lipoprotein and leukocyte accumulation in the
vessel wall. With some exceptions, all leukocytes are produced in the bone marrow. Here, we
will explore long-distance communication between disease locations and hematopoiesis in the
bone marrow. We will identify factors secreted in the atheroma and ischemic myocardium, and
then target those factors whose cognate receptor is expressed by hematopoietic stem and
progenitor cells. Such an approach will reveal direct transmission lines by which effector sites
might control leukocyte production, mobilization, and function. In the first aim, we will screen for
secreted factors that link diseased cardiovascular microenvironments with the bone marrow. We
will perform RNAseq to generate data sets for myocardial infarction and atherosclerosis to
identify ligand-receptor pair expression in the same milieu. For promising candidates, we will
confirm mRNA expression and protein expression with available tools. For each candidate
molecule, we will follow the blueprint established with our preliminary data, adapting the strategy
to profile how other factors produced in atherosclerotic lesions and in the infarcted myocardium
might influence the bone marrow. In the second aim, we will elucidate long-distance
mechanisms by which diseased microenvironments exert remote control of the bone marrow.
We will determine how candidate factors produced in the atherosclerotic lesion and in the
infarcted myocardium control processes in the bone marrow. Collectively, these experiments will
identify new lines of long-distance communication between diseased sites (lesion, infarct),
elucidate the underlying mechanisms, and pave the way for new therapeutic approaches for
cardiovascular disease.

## Key facts

- **NIH application ID:** 10238043
- **Project number:** 5P01HL142494-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Filip K Swirski
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $399,886
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238043

## Citation

> US National Institutes of Health, RePORTER application 10238043, Project 3:  Remote control of hematopoiesis in cardiovascular disease (5P01HL142494-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10238043. Licensed CC0.

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