# A Novel Role for cMyc in Vascular Homeostasis

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $522,936

## Abstract

Endothelial cells play an important role in the maintenance of tissue homeostasis. Endothelial dysfunction,
characterized by phenotypic and hemodynamic changes in blood vessels, is an early predictor of cardiovascular
disease, the leading cause of death worldwide. Chronic oxidant injury to the endothelium during aging leads to
endothelial senescence and development of a pro-inflammatory phenotype, increasing the risk of cardiovascular
events such as myocardial infarction and stroke. Therefore, better understanding of the molecular mechanisms
that regulate vascular aging and inflammation, is essential for the control of cardiovascular disease. The
endothelium plays a critical role in inflammation by controlling the expression of cytokines and adhesion
molecules involved in attraction, adhesion and infiltration of inflammatory cells. Consistent with the systemic
distribution of the vascular network, endothelial cells are a potential source of inflammatory mediators in aging
and chronic-inflammatory diseases. Although the identity of pro-inflammatory molecules is well known, the
mechanisms that control their expression are complex and multifactorial. Therefore, more studies are needed to
identify cellular mediators as well as central molecules and pathways that regulate senescence pro-inflammatory
response under normal aging and pathological conditions.
Our long-term goal is to develop interventions to preserve endothelial homeostasis, thus preventing vascular
inflammation and associated cardiovascular disease. Our goal with the proposed study is to understand how
endothelial cMyc regulates vascular aging and inflammation. Recent work from our group have identified a novel
role for the transcription factor cMyc as a potential regulator of vascular senescence and inflammation. Our
preliminary studies indicate that cMyc expression declines in human endothelial cells undergoing replicative
senescence, and that this phenomenon is associated with increased expression of inflammation markers. We
performed gene expression profiling studies in mice overexpressing cMyc specifically in endothelial cell lineage
and observed a reduction in the expression of the senescence marker p21 and pro-inflammatory mediators with
aging in different organs. These findings support the central hypothesis that cMyc is an essential regulator of
senescence-associated vascular inflammation. In Aim 1, we will determine how cMyc regulates vascular aging
using wild-type and genetically engineered adult mice with conditional deletion of c-Myc specifically in endothelial
lineage. In Aim 2, we will investigate the contribution of cMyc to vascular inflammation using the mouse model
described in Aim 1. In Aim 3, we will identify cMyc downstream target genes that play a role in vascular aging
and inflammation. For the 3 aims proposed, results will be compared to commercially available endothelial cells
from young and aged donors. Completion of these aims will define novel mechanisms and p...

## Key facts

- **NIH application ID:** 9985631
- **Project number:** 5R01HL128536-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** CLAUDIA RODRIGUES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $522,936
- **Award type:** 5
- **Project period:** 2017-08-10 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985631

## Citation

> US National Institutes of Health, RePORTER application 9985631, A Novel Role for cMyc in Vascular Homeostasis (5R01HL128536-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9985631. Licensed CC0.

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