# Lipoprotein Interactions in the Vessel Wall

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $548,924

## Abstract

PROJECT SUMMARY
There is a critical need to stop atherosclerosis initiation and progression, rather than trying to treat its progression
in an advanced state. It is widely recognized that entry and retention of low density lipoproteins (LDL) are key
steps in atherogenesis. However, our data show high density lipoproteins (HDL) can compete with LDL to bind
SR-BI and HDL can interact with LDL to decrease binding to proteoglycans. With the recent realization that
lipoproteins, both LDL and HDL, exist a series of related but compositionally distinct subpopulations, new
questions have arisen as to how lipoprotein subspeciation may affect these igniting steps of atherosclerosis.
This work builds on data generated under PI Shah’s K award (K23HL118132) showing that 1) HDL and LDL
exist as multiple subspecies, 2) specific HDL subspecies, their amount, composition (lipids, proteins) and
function are altered in the plasma of individuals with type 2 diabetes, and 3) the amount of large HDL subspecies
in plasma are inversely correlated with early markers of cardiovascular risk. This proposal also builds on our
preliminary data that shows HDL modulates both LDL transcytosis and binding to proteoglycans, but this is
disrupted in the context of type 2 diabetes. Our overarching hypothesis that that LDL and HDL subspecies
differentially impact transcytosis and proteoglycan binding and disruption of their balance in type 2 diabetes
contributes to the high risk of cardiovascular disease in this population. Using complementary approaches that
include in-vitro cell based assays with animal models and patient samples in adolescents and adults, we aim to
identify and characterize the LDL and HDL subspecies involved in endothelial cell transcytosis (Aim 1) and
extracellular proteoglycan binding (Aim 2) and to understand the impact of type 2 diabetes on these lipoprotein
subspecies (Aim 3). These results have the potential to inform future therapeutic strategies to use recombinant
particles or mimetic peptides to prevent atherosclerosis initiation. The ability to block atherosclerosis initiation
and progression will benefit both youth and adults, and particularly individuals with type 2 diabetes who are at
increased risk for cardiovascular disease.

## Key facts

- **NIH application ID:** 10375568
- **Project number:** 5R01HL157260-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** W Sean Davidson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $548,924
- **Award type:** 5
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375568

## Citation

> US National Institutes of Health, RePORTER application 10375568, Lipoprotein Interactions in the Vessel Wall (5R01HL157260-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10375568. Licensed CC0.

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