# Role of Protein Tyrosine Phosphatase 1B in Cardiac Hypertrophy

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT ALBANY · 2024 · $566,357

## Abstract

Project Summary
Oxidative stress is associated with reduced left ventricular (LV) function and correlates with the severity of heart
failure in patients. We have recently demonstrated that Protein Tyrosine Phosphatase 1B (PTP1B) becomes
reversibly oxidized and inactivated in pressure overload-induced cardiac hypertrophy and that PTP1B
inactivation causes profound changes in thyroid hormone responsiveness. We showed that inhibiting the
synthesis of triiodothyronine (T3) rescued the exacerbated pressure overload-induced hypertrophy and improved
myocardial contractility and systolic function in cardiomyocyte-specific PTP1B knockout mice (PTP1B cKO). We
hypothesize that as hypertrophy develops, the inhibition of the cardioprotective activity of PTP1B by cellular
oxidants leads to T3-mediated changes contributing to pathological hypertrophy. Based on our recently
published data in which we demonstrate that breaking the interaction between 14-3-3ζ and PTP1B prevents its
inactivation in vivo, we also hypothesize that ectopic expression of a peptide derived from PTP1B, will both
prevent the oxidation and inactivation of PTP1B in myocytes, and prevent pathological thyroid hormone
signaling, left ventricular hypertrophy and heart failure. We propose the following specific aims to test this
hypothesis.1) Determine the molecular mechanisms controlling PTP1B oxidation and downstream thyroid
hormone signaling in cardiac hypertrophy. 2) Investigate the potential therapeutic and anti-hypertrophic effects
of a novel PTP1B peptide that destabilizes the oxidized form of PTP1B and increases its catalytic activity in vivo.
Understanding how PTP1B regulates thyroid hormone-mediated hypertrophy will provide critical insight into
molecular mechanisms involved in cardiac hypertrophy and lead to novel strategies of therapeutic intervention
in heart failure.

## Key facts

- **NIH application ID:** 10972710
- **Project number:** 1R01HL175391-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT ALBANY
- **Principal Investigator:** Benoit Boivin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $566,357
- **Award type:** 1
- **Project period:** 2024-06-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10972710

## Citation

> US National Institutes of Health, RePORTER application 10972710, Role of Protein Tyrosine Phosphatase 1B in Cardiac Hypertrophy (1R01HL175391-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10972710. Licensed CC0.

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