# The Role of Osteopontin-OGDHL Axis in HFpEF

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $437,820

## Abstract

SUMMARY
Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent and complex syndrome for
which no etiological therapy is available. Osteopontin (OPN) is a matricellular protein that induces mitochondrial
damage and oxidative stress in cardiac myocytes. OPN is upregulated in the circulation of HFpEF patients. Our
work and preliminary data show that the Col4a3-/- mice, a model of kidney disease, display a HFpEF phenotype
that includes cardiac diastolic dysfunction, hypertrophy, fibrosis, hypertension, and elevated renal and plasma
levels of OPN. Our preliminary data reveals that mRNA and protein levels of 2-Oxoglutarate Dehydrogenase-
Like (OGDHL), a Krebs cycle isoenzyme involved in OGDH complex formation and mitochondrial energy
metabolism, is decreased in Col4a3-/- hearts. We found that double knockout Col4a3-/-OPN-/- mice have elevated
cardiac OGDHL protein levels, and improved HFpEF phenotype. Dysregulated myocardial energetics in HFpEF
patients is known to be a major contributor to disease progression. Therefore, using small and large animal
models of HFpEF, we will test the hypothesis that upregulated OPN, released from the kidney, activates
pathological signaling in the heart causing a decline in OGDHL and related ATP production contributing to the
observed HFpEF phenotype in Col4a3-/- mice.

## Key facts

- **NIH application ID:** 9849803
- **Project number:** 5R01HL140468-03
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Lina A Shehadeh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $437,820
- **Award type:** 5
- **Project period:** 2018-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849803

## Citation

> US National Institutes of Health, RePORTER application 9849803, The Role of Osteopontin-OGDHL Axis in HFpEF (5R01HL140468-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849803. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*