# The role of endothelial ActRII signaling in age-related Heart Failure with preserved Ejection Fraction (HFpEF)

> **NIH NIH K01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $129,330

## Abstract

PROJECT SUMMARY/ABSTRACT
The following proposal is submitted by Dr. Peng Xia, PhD, in response to PA-20-190. Dr. Xia is currently a NIH
T32 fellow in the Massachusetts General Hospital Cardiovascular Research Center (MGH CVRC). Since his
initial K01 submission, he has been promoted to Instructor in Medicine at Harvard Medical School (HMS). Here,
Dr. Xia proposes a comprehensive 5-year program of career development and mentored research to achieve
his long-term career goals of 1) becoming an independent investigator in cardiovascular aging biology and 2)
developing novel therapeutics for older adults with cardiovascular disease. To accomplish these goals, Dr. Xia
will be primarily mentored by Dr. Paul Yu, MD, PhD, Director of the MGH CVRC and an internationally-recognized
expert in vascular and Activin biology. Dr. Xia will also be co-mentored by Dr. Jason Roh, MD, MHS (NIA Beeson
scholar, Cardiac aging expert) and Dr. Aaron Aguirre, MD, PhD (advanced imaging expert). His training will be
supplemented by a Scientific Advisory Committee, including Drs. Jennifer Ho, MD, Ariela Orkaby, MD, MPH,
and Anthony Rosenzweig, MD, who will provide complementary expertise in cardiac aging, heart failure, and
frailty biology. Dr. Xia will conduct his research in the world class scientific environments of the MGH CVRC and
HMS, and will actively engage in the rich local and national aging research communities outlined in his training
plan. The plan has been specifically designed to advance Dr. Xia’s knowledge base and scientific skills in this
new area of investigation for him, and foster his development as a future leader in cardiovascular aging science.
Dr. Xia has generated most of the preliminary data that provides the foundation for this innovative proposal. Here,
he seeks to investigate a potential causal role of endothelial Activin type II receptor (ActRII) signaling in age-
related heart failure with preserved ejection fraction (HFpEF). His overarching hypothesis is that pathological
aging upregulates endothelial ActRII signaling, which induces the hallmark cardiac microvascular rarefaction and
inflammatory phenotypes observed in HFpEF. This work has high translational potential with ActRII inhibitors
being FDA-approved for other clinical indications. The significance of this work is also highlighted by 1) HFpEF
being a leading cause of morbidity and mortality in older adults, and 2) the limited therapeutic options for this
prevalent geriatric HF syndrome. In this proposal, Dr. Xia will rigorously study the functional role of endothelial
ActRII signaling in age-related HFpEF in 3 aims. Aim 1 is designed to determine if age-associated endothelial
ActRII activation contributes to cardiac dysfunction in HFpEF; Aim 2 will utilize advanced imaging methods to
determine if endothelial ActRII activation induces microvascular rarefaction and inflammation; and Aim 3 will
elucidate the molecular mechanism(s) underlying endothelial cell ActRII signaling in age-relate...

## Key facts

- **NIH application ID:** 10929465
- **Project number:** 5K01AG080077-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Peng Xia
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $129,330
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929465

## Citation

> US National Institutes of Health, RePORTER application 10929465, The role of endothelial ActRII signaling in age-related Heart Failure with preserved Ejection Fraction (HFpEF) (5K01AG080077-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10929465. Licensed CC0.

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