# Role of Endothelial Cell Metabolism in Cardiovascular Disease and the Atheroprotective Effects of Chronic Exercise

> **NIH NIH F31** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $32,237

## Abstract

Project Summary/Abstract
This proposed training plan will provide high-quality professional development for the applicant through the
pursuit of experiments designed to determine the impact of chronic exercise, physical inactivity, and
cardiovascular disease on mechanisms that mediate endothelial cell function, with the goals of addressing a
critical barrier to our current understanding of cardiovascular disease and eventual application of these
mechanisms towards the clinical treatment and prevention of cardiovascular disease. The isoenzyme 6-
phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) regulates glycolytic metabolism and is
essential for endothelial cell function. Understanding the role of PFKFB3 in endothelial cell metabolism and
function has recently emerged, and as a result the current literature merely describes the effect of
cardiovascular disease on perturbations in endothelial cell metabolism and function. Research identifying the
mechanisms underlying the development of cardiovascular disease-induced deregulations in endothelial cell
metabolism and function are non-existent. Indeed, a lack of chronic exercise (physical inactivity) reduces
endothelial function and increases the risk for cardiovascular disease, whereas chronic exercise training
ameliorates cardiovascular disease risk and enhances vascular function. The possibility that chronic exercise
may confer protection against cardiovascular disease through functional adaptations in endothelial cell
metabolism has not been addressed. Therefore, the overall goal of the present application, in combination with
carefully integrated career development activities and mentors with expertise in biology, cell metabolism, and
exercise physiology, is to describe the extent to which endothelial metabolism mediates the function of
endothelial cells across a spectrum of cardiovascular disease risk, from the atheroprotective effects conferred
through chronic exercise at one end, to the physical inactivity-induced manifestation of endothelial dysfunction
in the middle, to overt cardiovascular disease on the other end as an extreme. Serum samples collected from
individuals who perform chronic exercise, physically inactive but healthy participants, and patients with overt
cardiovascular disease will be cultured on human umbilical vein endothelial cells to isolate the effect of
circulating factors on endothelial cell metabolism and function. In the final set of experiments, serum from the
aforementioned populations will be cultured on human umbilical vein endothelial cells with PFKFB3 either
overexpressed or knocked down to determine how alterations in endothelial cell metabolism mediate
endothelial cell function across the spectrum of cardiovascular disease risk. Identifying the role of endothelial
metabolism in vascular homeostasis will have far broader implications than exercise alone, with the results of
the proposed experiments addressing a critical barrier to our current unders...

## Key facts

- **NIH application ID:** 9844480
- **Project number:** 5F31HL140777-03
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Daniel D. Shill
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,237
- **Award type:** 5
- **Project period:** 2018-01-15 → 2021-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844480

## Citation

> US National Institutes of Health, RePORTER application 9844480, Role of Endothelial Cell Metabolism in Cardiovascular Disease and the Atheroprotective Effects of Chronic Exercise (5F31HL140777-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9844480. Licensed CC0.

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