# HL-Regulation of Angiogenesis in the Obese Adipose Tissue by Secreted microRNAs

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $526,339

## Abstract

PROJECT SUMMARY
HL-142: Obesity and its accompanying metabolic disorders represent the great public health
challenge of our time and is considered an independent risk factor for cardiovascular disease
(CVD). Adipose tissue (AT) expansion and remodeling is an ongoing process that is pathologically
altered in the obese state, which is characterized by increased pro-inflammatory state, inadequate
angiogenic response and fibrosis. Although adipocytes are key players orchestrating local changes
in the microenvironment, much evidence also points towards a pivotal role for macrophages in
such remodeling events, by affecting both adipocyte and endothelial cell (EC) angiogenic
functions. Because angiogenesis is a rate-limiting step for AT remodeling, it is essential to
understand the crosstalk between macrophages and ECs. It is accepted that obesity is
accompanied by a change in the composition of macrophages, from an anti-inflammatory and
angiogenic form, to a highly inflammatory form responsible for the negative outcomes that arise
from obesity. Important players of the post-transcriptional regulatory network are the small non-
coding RNAs, microRNAs (miRNAs), which have a demonstrated role in the control of
transcriptional networks in MΦs. Intriguingly, miRNAs can be transferred from cell to cell by
exosomes, thus facilitating the exchange of information among cells. The molecular composition
and content of exosomes may vary depending on whether the secretion is constitutive or a
consequence of cell activation. We hypothesize that in obese AT, activated macrophages produce
exosomes that contain a specific set of miRNAs that target ECs modulating their function, by
controlling gene expression and therefore affecting AT expansion and remodeling. This project will:
answer important questions regarding exosome specificity and function; provide critical insights
into the contribution of macrophage-derived microRNAs as vehicles of paracrine communication
between macrophage and ECs in the regulation angiogenesis in the AT. These findings will pave
the way to the identification of innovative therapeutic strategies to modulate AT expansion and
remodeling during obesity.

## Key facts

- **NIH application ID:** 9872197
- **Project number:** 5R01HL135012-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Yajaira Suarez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $526,339
- **Award type:** 5
- **Project period:** 2017-06-15 → 2021-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872197

## Citation

> US National Institutes of Health, RePORTER application 9872197, HL-Regulation of Angiogenesis in the Obese Adipose Tissue by Secreted microRNAs (5R01HL135012-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9872197. Licensed CC0.

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