# Macrophages in homeostasis and cardiovascular disease

> **NIH NIH R35** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $358,265

## Abstract

Macrophages inhabit all major organs. These large phagocytic myeloid leukocytes' primary purpose may be to
maintain tissue integrity by ingesting and eliminating dangerous or dispensable material. From clearing
bacteria to pruning neurons, macrophages adapt their functions to meet the needs of their home tissues. The
recent recognition that tissue macrophages derive from different sources, coupled with the idea that
environmental cues and inflammatory stimuli can sculpt and agitate homeostatic order, provides a frame of
reference from which we can decipher the breadth and depth of macrophage activity. Here, I will use: (i)
models of atherosclerosis (Ldlr–/–, Apoe–/–, PCSK9-Ad) and myocardial infarction (permanent ligation, ischemia
reperfusion); (ii) environmental stimuli (diet, sleep fragmentation); (iii) transgenic and knockout mice
(Cx3cr1CreERT2 R26-tdT, IL-3–/–, Csf2–/–, Csf2rb–/–, CD123–/–); (iv) surgical procedures (parabiosis, spleen
transplantation); (v) real-time imaging technologies (PET-MRI, intravital microscopy); and (vi) many
immunology and molecular biology techniques to investigate macrophage development and function in
cardiovascular disease. In aggregate, these tools will allow to decipher how macrophages of different orgins
(yolk sac, fetal liver, adult bone marrow, adult spleen, vascular smooth muscle cells) and in different locations
(adventitia, intima, ischemic myocardium, remote myocardium) collaborate with and differ from one another
during atherosclerosis and its complications. A central concept of this grant is the tension between macrophage
ontogeny as a determinant of macrophage function and the idea that tissues condition macrophage activities
and supplant the influence of macrophage ontogeny in favor of environmental demands.

## Key facts

- **NIH application ID:** 10114312
- **Project number:** 5R35HL135752-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Filip K Swirski
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $358,265
- **Award type:** 5
- **Project period:** 2017-03-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114312

## Citation

> US National Institutes of Health, RePORTER application 10114312, Macrophages in homeostasis and cardiovascular disease (5R35HL135752-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10114312. Licensed CC0.

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