# Troponin I phosphorylation as a novel novel cardiac inotrope

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $700,742

## Abstract

PROJECT SUMMARY
In heart disease, the amount of blood pumped by the heart is not sufficient to supply the metabolic demands of
the body. Current positive inotropes (dobutamine, milrinone) increase cardiac contraction by elevating the
intracellular calcium contractile signal, however trials have demonstrated this elevated intracellular calcium also
causes detrimental arrhythmia, impaired relaxation, and increased mortality rendering this inotropic approach
unsuccessful as a long-term therapy. There are currently no approved therapies that directly increase the
insufficient function of the heart in disease without long-term detrimental effects. The myofilament protein
troponin I (TnI) is critical to relay the calcium activating signal into muscle contraction and is therefore a key
regulator of in vivo cardiac muscle function. We have shown the site-specific phosphorylation of TnI increases
cardiac muscle contraction without elevating intracellular calcium. Our preliminary data now demonstrates this
TnI phosphorylation increases in vivo cardiac function in both normal and diseased hearts without long-term
detrimental effects. This proposal will establish the novel effects and mechanism of this TnI site-specific
phosphorylation to improve in vivo cardiac function in the normal and diseased mouse heart. We will further
establish the effects and safety of this site-specific TnI phosphorylation on human cardiac tissue towards
establishing this phosphorylation as a future therapeutic approach in human heart disease.

## Key facts

- **NIH application ID:** 10818545
- **Project number:** 5R01HL164795-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Brandon J Biesiadecki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $700,742
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818545

## Citation

> US National Institutes of Health, RePORTER application 10818545, Troponin I phosphorylation as a novel novel cardiac inotrope (5R01HL164795-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10818545. Licensed CC0.

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