# Genomic and Proteomic Architecture of Atherosclerosis

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $2,113,515

## Abstract

Project Summary
At the molecular level atherosclerosis can be defined as an assembly of hundreds of intra- and extra-cellular
proteins that jointly alter cellular processes and remodel the local environment in characteristic ways.
Proteomic changes produce vascular lesions responsible for ischemic cardiovascular events worldwide.
Unfortunately, current methods to treat and prevent cardiovascular disease focus on risk factors that are not
deterministic of these proteomic changes; or on anatomic manifestations of the disease that are evident long
after the proteomic changes are underway. To detect disease early and interrupt the disease process before
clinical consequences occur, it is necessary to recognize and understand the specific patterns of arterial
proteins that constitute the molecular signature of atherosclerosis. Indeed, if these arterial protein changes
could be reliably detected and reversed, the possibility of eradication of coronary, cerebral and peripheral
arterial disease would be within our grasp. Thus, the long-term goal of our research group is to
comprehensively define the proteomic architecture of atherosclerosis, to develop reliable methods to
detect these changes, and ultimately to identify mechanisms to prevent or reverse them.
In the initial funding (GPAA Phase 1, 2012-2016) our group capitalized on advances in applied proteomics and
new analytic methods to develop a clinical, technical and analytic platform to study the human arterial
proteome. This work produced clear evidence that early atherosclerotic plaques are characterized by complex
changes in the proteomic topology of several cell regulatory pathways. Our current goal is to extend this work
to include robust descriptions of the proteomic architecture of atherosclerosis specifically in women and
African-Americans, to expand the portfolio of protein features, and develop a multi-dimensional clinical assay
that could be used for early detection. To achieve this goal we propose the following Specific Aims:
1. Validate and expand the atherosclerosis-associated protein profiles identified in GPAA in
additional autopsy specimens and determine if these profiles vary as a function of sex or
ethnicity.
2. Identify protein isoforms and selected PTM proteins that are enriched in atherosclerotic plaques
and define significant downstream protein networks.
3. Based on our data, develop and produce a plasma protein biomarker panel to predict the presence
of subclinical atherosclerosis and risk for future cardiovascular events.
The resulting data will provide novel insights into the pathogenesis of atherosclerosis and support the
development of a new clinical tool that should be useful for improved prediction and pre-clinical assessment of
therapeutic efficacy of current and novel future interventions.

## Key facts

- **NIH application ID:** 10130591
- **Project number:** 5R01HL111362-08
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** DAVID McLeod HERRINGTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,113,515
- **Award type:** 5
- **Project period:** 2012-07-18 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130591

## Citation

> US National Institutes of Health, RePORTER application 10130591, Genomic and Proteomic Architecture of Atherosclerosis (5R01HL111362-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130591. Licensed CC0.

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