# Structure-Function Analysis of Triglyceride Regulator ApoA-V Using Natural Variants

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $745,884

## Abstract

PROJECT SUMMARY
Hypertriglyceridemia (hyperTG) is common and is causally associated with at least two important medical
consequences: recurrent acute pancreatitis when TGs are extremely elevated and atherosclerotic cardiovascular
disease (CVD) across a wide range of elevated TGs. Both of these represent unmet medical needs, as current
approaches to reducing TGs are often insufficient in reducing extremely elevated TGs, preventing pancreatitis,
and/or reducing cardiovascular disease (CVD) risk. These observations emphasize the need for novel therapies
to reduce TGs and the clinical sequelae of hyperTG and elevated triglyceride-rich lipoproteins (TRLs). Human
genetics studies indicate that TRLs are causally related to risk of pancreatitis and CVD, and have identified a number
of potential therapeutic targets. In this project we focus on ApoC-III and ApoA-V, which are genetically validated
and reciprocally modulate LPL activity, thereby influencing triglyceride levels and risk of pancreatitis and CVD. This
proposal will build upon our work in the current grant cycle and will provide new information regarding ApoA-V and its
reciprocal relationship with ApoC-III, as well as enhance the development of ApoA-V based therapeutic strategies
to reduce the clinical consequences of elevated TGs and TRLs. We will derive a detailed understanding of the
structure-function relationships of ApoA-V and gain greater insight into the mechanisms by which ApoA-V enhances
LPL and possibly reduces VLDL secretion. This information will be highly relevant to informing the development of
translational therapies that target ApoA-V with the goal of reducing elevated triglycerides and the clinical sequelae of
acute pancreatitis and atherosclerotic CVD.

## Key facts

- **NIH application ID:** 10211481
- **Project number:** 2R01HL133502-05A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Daniel James Rader
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $745,884
- **Award type:** 2
- **Project period:** 2016-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10211481

## Citation

> US National Institutes of Health, RePORTER application 10211481, Structure-Function Analysis of Triglyceride Regulator ApoA-V Using Natural Variants (2R01HL133502-05A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10211481. Licensed CC0.

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