# AGING & VASCULAR DISEASE ROLE OF GLYCATION

> **NIH NIH R01** · PICOWER INSTITUTE FOR MEDICAL RESEARCH · 1993 · $189,311

## Abstract

DESCRIPTION (Adapted from Applicant's Abstract):  Progressive thickening,
loss of elasticity, and occlusion of small and large blood vessels occurs
as a part of the normal aging process with, or independently of,
atherosclerosis.  Because diabetes accompanies normal aging frequently, and
shares many of the typical features of aging vasculopathy, it is accepted
that its presence severely accelerates the effects of aging alone.
Advanced Glycosylation Endproducts (AGE) are nonenzymatically glycosylated
adducts of proteins accumulating in vascular tissues with aging, and at an
accelerated rate in diabetes.  The investigators have recently demonstrated
that endothelial cells (EC) express a specific cell surface binding site
for AGEs which, upon interaction with the ligand, mediates transcytosis of
AGEs to the subendothelium, induces increased permeability and enhances EC
pro-coagulant properties.  These observations, in connection with the known
abundance of AGEs in aged and diabetic vascular tissues, indicate that
AGE-EC interactions may be crucial for the development of age and diabetes
related vascular pathology.  The objectives of this proposal are aimed at
the elucidation of the response of vascular endothelium to AGEs by
examining:  1) The nature of the AGE-binding site on endothelium, and its
relationship to the recently identified AGE-receptor on macrophages.
Purification of the receptor molecule, cloning of the receptor gene, and
development of poly- and mono-clonal antibodies, and cloning of the
receptor gene, will allow assessment of its functional properties and cell
surface and tissue distribution.  2) The cellular processing and deposition
of AGEs in subendothelial matrix.  3) The in vivo relevance of these
observations, and their correlation to the progression of the diabetic
and/or aging process, utilizing animal models.  The first 2-3 years will be
devoted largely to aims 1 and 2 while during the last two years the
potential relationship of this system to in vivo relevant processes will be
addressed.

The interactions of this endothelial receptor with glucose-modified
AGE-proteins may be biologically significant, as they involve a protein
modification known to form abundantly in vivo.  While the AGE-receptor
system may normally function toward the selective disposal of modified
macromolecules under conditions of enhanced tissue AGE accumulation, as it
occurs in aging and diabetes, it may mediate vascular dysfunction, such as
progressive occlusion, permeability and thrombotic diathesis, typically
seen in the elderly and the diabetic patient.

## Key facts

- **NIH application ID:** 3121312
- **Project number:** 5R01AG009453-03
- **Recipient organization:** PICOWER INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** HELEN VLASSARA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $189,311
- **Award type:** 5
- **Project period:** 1992-01-15 → 1996-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121312

## Citation

> US National Institutes of Health, RePORTER application 3121312, AGING & VASCULAR DISEASE ROLE OF GLYCATION (5R01AG009453-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121312. Licensed CC0.

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