# Mitochondrial therapy in conjunction with guideline directed medical therapy in cardiomyopathy

> **NIH NIH F32** · STANFORD UNIVERSITY · 2024 · $86,488

## Abstract

PROJECT SUMMARY
Heart failure (HF) is the leading diagnosis of hospital admission in the US. Despite significant advances in
medical therapies during the last three decades, HF remains one of the leading causes of mortality and
morbidity worldwide. Cardiac tissue from patients with cardiomyopathy exhibits mitochondrial structural
abnormalities. Current guideline-directed medical therapy (GDMT) in HF, including beta-blockers and renin–
angiotensin-aldosterone (RAS) antagonism, reduces cardiac workload and helps in cardiac remodeling, but
their impact on the mitochondria is not known. New therapies are needed. Stem cell-derived mitochondria-
based technologies offer a novel approach to myocardial protection and repair, and their potential interaction
with current gold-standard therapy also needs to be studied for successful translation.
This proposal presents a study using both GDMT and mitochondria-rich extracellular vesicles (M-EVs) to
transfer their mitochondria into injured cardiomyocytes and myocardium to improve viability and function in HF.
In my first aim, I will determine the mechanism of the protective effects of M-EVs in combination with GDMT by
adapting an innovative induced cardiomyocyte (iCM) model of hypoxic injury. To test this, iCMs will be treated
with combinations of beta blockers, RAS antagonists, M-EVs, and combinations of GDMT and M-EVs. iCM
function and viability will then be rigorously assessed. In the second aim, the functional benefits of the M-EVs
and GDMT will be studied in a mouse model. I will study the effects of combined therapy on mitochondrial
augmentation and biogenesis by looking at proteomic and metabolomic profiles of the injured myocardium in
relation to a key regulator, PGC-1α. This proposed study will improve our understanding of the interaction of
mitochondria-based therapies with existing heart failure therapies and give critical insight into the future
development of much-needed novel therapies.

## Key facts

- **NIH application ID:** 10997199
- **Project number:** 1F32HL176108-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jiwen Li
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $86,488
- **Award type:** 1
- **Project period:** 2024-09-13 → 2026-09-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997199

## Citation

> US National Institutes of Health, RePORTER application 10997199, Mitochondrial therapy in conjunction with guideline directed medical therapy in cardiomyopathy (1F32HL176108-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10997199. Licensed CC0.

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