# The Role of High Density Lipoprotein Associated Protease Inhibitor Activity in Protection Against Atherosclerosis.

> **NIH NIH K22** · UNIVERSITY OF KENTUCKY · 2020 · $240,629

## Abstract

Project Summary and Abstract
High density lipoproteins (HDL) have a well-established inverse correlation with the occurrence of
cardiovascular disease. However, the functional activities of HDL which mediate this protection are
not well understood. HDL are micellar complexes composed of lipids and an array of different
proteins which are likely to confer specific functions to the HDL particles that carry them. Of more
than 85 identified HDL associated proteins, over 20% have known functions related to protease
inhibition, the majority of these are members of the Serine Protease Inhibitor (SERPIN) family of
proteins. This proposal will examine the structural interaction between the most abundant HDL-bound
SERPIN, alpha-1-antitrypsin (A1AT), and HDL particles and also the functional consequences of this
interaction. Dr. Gordon will use individual particle electron tomography, a novel molecular imaging
technique, to determine the structural details of the interaction between A1AT and HDL and to identify
the region of the A1AT protein involved in binding. Using reconstituted HDL, enriched with A1AT, Dr.
Gordon will investigate the capacity of these particles to reduce vascular protease activity and
subsequent atherosclerosis development in a mouse model. Additionally, a novel HDL targeting small
peptide mimetic of A1AT will be developed and evaluated for its capacity to prevent atherosclerosis
development and to stabilize existing plaque in an effort to prevent thrombus formation and
subsequent cardiovascular events such as heart attack, stroke, or pulmonary embolism.
 This work has been proposed by Dr. Scott Gordon, a postdoctoral fellow of the National Heart,
Lung, and Blood Institute at the National Institutes of Health, as part of an NHLBI K22 Career
Transition Award. Dr. Gordon performed his graduate studies on the composition and function of HDL
and has extended his previous work in the current proposal. A team of experienced mentors with a
variety of skills related to aspects of this proposal has been assembled by Dr. Gordon to assist in the
successful completion of the proposed research as well as the successful transition of Dr. Gordon
into an independent tenure track academic faculty position at a major research university in the
United States.

## Key facts

- **NIH application ID:** 9983143
- **Project number:** 5K22HL141299-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Scott M Gordon
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $240,629
- **Award type:** 5
- **Project period:** 2018-08-20 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983143

## Citation

> US National Institutes of Health, RePORTER application 9983143, The Role of High Density Lipoprotein Associated Protease Inhibitor Activity in Protection Against Atherosclerosis. (5K22HL141299-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9983143. Licensed CC0.

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