# Shedding of Endothelial Glycocalyx in Morbidly Obese Patients

> **NIH NIH R00** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $148,415

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Mohamed, Abeer
PROJECT SUMMARY (See instructions):
 Obesity is a growing global epidemic and healthcare burden. The cardiovascular risk associated
with obesity is well-documented, yet specific pathophysiological mechanisms are poorly
understood. The broad, long term goal of my currently funded R00 application is to identify valid
targets and strategies for the prevention and treatment of obesity-related cardiovascular disease
(CVD). The central hypothesis in my R00 application was that tissue hypoxia in obese subjects
results in dysfunctional perivascular adipocytes that secrete lots of inflammatory mediators and
adversely affect vascular function. Data from my current study demonstrated augmented production
of heparinase by adipocytes isolated from obese subjects compared with non-obese controls.
Heparinase is an enzyme that degrades the endothelial cell glycocalyx, which is a carbohydrate-
rich layer that lines the vascular endothelium and plays a critical role in maintaining several aspects
of vascular homeostasis. Accordingly, we propose that the impaired vascular function we observed
in the arterioles isolated from obese subjects could be, at least in part, attributed to the induction of
adipocyte-derived heparinase and the disruption of endothelial glycosylation. Thus, the primary
objective of the present supplemental proposal is to investigate endothelial glycocalyx shedding
from the arteriolar surface and its subsequent enrichment in the circulation. In the current R00
project, we study the microvasculature of morbidly obese subjects, which makes us well-poised to
employ the CF-GSP glycoscience tools to advance our understanding of disturbed endothelial
glycosylation as an integral aspect of obesity-related CVD. Our central hypothesis is that the
induced heparinase secretion by the hypoxic, dysfunctional adipose tissues in obese individuals is
targeting the heparan sulfate glycosaminoglycans in the endothelial glycocalyx resulting in its
degradation and eventually, dysregulation of vascular glycobiology. We will test this hypothesis by
pursuing the following specific Supplementary Aim: Test the effectiveness of exercise and surgery-
induced weight loss on restoring endothelial glycocalyx integrity and circulating heparan sulfate
glycosaminoglycans in morbidly obese individuals.
RELEVANCE (See instructions):
The current study will improve our mechanistic understanding of the biological underpinning of
endothelial dysfunction in obesity. This study may identify circulating heparan sulfate
glycosaminoglycans as novel preventive and therapeutic targets for improving vascular function in
morbidly obese individuals.

## Key facts

- **NIH application ID:** 10135635
- **Project number:** 3R00HL140049-04S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Abeer M Mohamed
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $148,415
- **Award type:** 3
- **Project period:** 2020-09-03 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135635

## Citation

> US National Institutes of Health, RePORTER application 10135635, Shedding of Endothelial Glycocalyx in Morbidly Obese Patients (3R00HL140049-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135635. Licensed CC0.

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