# Frequency-dependent modulation of cardiac myofilament function in health/disease

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $380,264

## Abstract

Project Summary
In human heart failure, patient-to-patient variability is extremely well known, but
extremely understudied. Relaxation disorders and aberrant force-frequency relationship
(FFR) are both primary hallmarks of heart failure, and thus it is critical we understand the
actual individual's dysfunction of these two parameters. It is imperative that we
understand the actual molecular events in an affected individual, and not the purported
molecular events that are based on group averages, that are known to be incorrect.
Since clinical assessment and treatment is done on the single individual level, in this
cycle of the grant we will work from the governing hypothesis that understanding of
patient-specific protein expression and post-translational modification will allow us to
understand the patient-specific relaxation dysfunction and aberrant FFR in failing human
myocardium. To correlate a patient-specific profile with relaxation and FFR dysfunction,
we propose to complete the following aims; 1) Continue procurement of failing and non-
failing human myocardium, and assess relaxation behavior and the force-frequency
relationship, 2) To assess individual protein levels and PTMs involved in the tri-modal
regulation of relaxation and frequency-dependent contractile activation in human
myocardium. We will assess levels and post-translational modifications in calcium-
handling proteins, proteins involved in myofilament calcium sensitivity, and proteins
involved in cross-bridge cycling kinetics, and 3) To assess the level of correlation
between protein expression patterns and myocardial relaxation and force-frequency
behavior in non-failing and failing human myocardium. Direct linking patient-specific
molecular events to the pathophysiological situation in that patient will allow to better
focus and target treatment of this debilitating disease.

## Key facts

- **NIH application ID:** 9973777
- **Project number:** 2R01HL113084-09
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** PAULUS ML JANSSEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,264
- **Award type:** 2
- **Project period:** 2012-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973777

## Citation

> US National Institutes of Health, RePORTER application 9973777, Frequency-dependent modulation of cardiac myofilament function in health/disease (2R01HL113084-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9973777. Licensed CC0.

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