# Transendothelial transport mediated modulations to the High Density Lipoprotein

> **NIH NIH SC3** · CALIFORNIA STATE UNIVERSITY LONG BEACH · 2020 · $110,625

## Abstract

Title: Transendothelial transport mediated modulations to the High Density Lipoprotein
Summary
 Despite the vast amount of literature that indicates low plasma levels of HDL-cholesterol (HDL-C) is a risk
factor for cardiovascular disease (CVD), the last decade has seen a paradigm shift in the concept that it may
not be HDL-C levels per se but the functionality of HDL that is a determining factor in CVD. The shift in focus is
in light of several studies that show that neither pharmacological nor genetic intervention to increase HDL-C
levels, lower the risk for CVD. Thus, there is a pressing need to fill the gap in knowledge regarding the role of
HDL in CVD from a mechanistic perspective and understand structure-function relationships in HDL.
 In the current proposal, we hypothesize that apolipoprotein (apo) AI and apoE3, two critical apos on HDL,
undergo structural alterations and post translational modifications (PTM) and that HDL undergoes particle
modulation as a consequence of transendothelial transport from plasma to the arterial intima with significant
functional penalties. We will test this hypothesis by interrogating structure-function changes to the HDL with
two specific aims: (1) Identify structural and proteomic alterations to the HDL associated with transendothelial
transport across aortic endothelial cells, and, (2) Determine changes in HDL function following transendothelial
transport. We will carry out spectroscopic analysis of reconstituted HDL (rHDL) bearing spatially sensitive
fluorescent probes at flexible locations on apoAI or apoE3 to obtain insight into conformational alterations
following transcytosis. Based on previous findings about oxidatively modified apoAI in atherosclerotic plaques,
we postulate that the apos are susceptible to oxidative modification during transcytosis. To address this, we
will determine PTM in transcytosed HDL, specifically on apoAI, apoE3 and selected proteins involved in
lipoprotein metabolism by mass spectrometry. We will also perform lipoproteomic analysis to identify changes
to the protein and lipid composition of transcytosed HDL. In an independent but complementary approach, we
will examine changes in two major functional effects of transcytosed HDL: its ability to promote cholesterol
efflux from macrophages, and, its antioxidant activity. Completion of these studies will significantly advance our
understanding of the relationship between structure/composition and the atheroprotective effect of HDL at the
vascular wall. The expected outcome of the proposed studies is to have a deeper understanding of
modulations in HDL that render it dysfunctional. Establishing this relationship will aid in development of HDL-
based therapies and identification of biomarkers of CVD risk.
 The research enhancement objectives of the PI are to: (i) develop expertise in HDL and endothelial cell
biology, (ii) increase competitiveness to apply for major external funding by publishing research findings, (iii)
strengt...

## Key facts

- **NIH application ID:** 9994931
- **Project number:** 5SC3GM105561-07
- **Recipient organization:** CALIFORNIA STATE UNIVERSITY LONG BEACH
- **Principal Investigator:** VASANTHY NARAYANASWAMI
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $110,625
- **Award type:** 5
- **Project period:** 2013-06-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994931

## Citation

> US National Institutes of Health, RePORTER application 9994931, Transendothelial transport mediated modulations to the High Density Lipoprotein (5SC3GM105561-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9994931. Licensed CC0.

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