# The contribution of perivascular adipose tissue macrophages to microvascular dysfunction in obesity

> **NIH NIH R01** · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · 2022 · $390,000

## Abstract

PROJECT SUMMARY
Obesity causes microvascular dysfunction. The mechanisms that underpin the initiation and progression of
microvascular dysfunction are not known. This fundamental gap is a problem because microvascular
dysfunction precedes, and likely contributes to, the development of insulin resistance, hypertension, and type-2
diabetes. The perivascular adipose tissue (PVAT) that surrounds vessels plays a physiological role in
regulating vascular function. Preliminary data from the applicant’s lab show that proinflammatory macrophages
within the PVAT mediate microvascular dysfunction in obesity, and that macrophages release redox species
that impinge on microvascular function by modulating crosstalk between vessel nitric oxide and the gaseous
signaling molecule hydrogen sulfide. The objective of the current proposal is to define the role of PVAT
macrophages in the initiation and progression of microvascular dysfunction during obesity. The objective will
be accomplished by testing the central hypothesis that proinflammatory macrophages drive microvascular
disease during obesity by infiltrating the PVAT and releasing reactive nitrogen species, which limits nitric oxide
bioavailability and increase contractility by depleting vessel hydrogen sulfide. Three specific aims are
proposed: aim 1 will define the contribution of PVAT inflammation to the initiation and progression of
microvascular disease; aim 2 identify the paracrine signal that mediates communication between PVAT-
macrophages and the microvasculature, and aim 3 will define mechanisms by which PVAT-macrophages
affect microvascular signal transduction. A diet-induced mouse model of obesity will be used in combination
with macrophage depletion and tissue-specific knockouts. A comprehensive in vivo and in vitro analysis of the
interaction between PVAT, macrophages, and microvasculature will be performed in both male and female
animals by integrating data from intravital microscopy, pressure myography, confocal imaging of live
mesenteric arteriolar segments, and metabolic analyses. Completion of these aims will establish a new
paradigm in which recruitment of proinflammatory macrophages to the PVAT is a major catalyzing event in the
development and progression of microvascular dysfunction.

## Key facts

- **NIH application ID:** 10326354
- **Project number:** 5R01HL142906-04
- **Recipient organization:** ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
- **Principal Investigator:** Carl White
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2019-01-19 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10326354

## Citation

> US National Institutes of Health, RePORTER application 10326354, The contribution of perivascular adipose tissue macrophages to microvascular dysfunction in obesity (5R01HL142906-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10326354. Licensed CC0.

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