Wednesday, October 22, 2025 10/22/2025

Sex-dependent regulation of cardiac cAMP, ECC, and arrhythmia by phosphodiesterases

Award Number: R01HL179122
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/09/2025
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Sex-dependent regulation of cardiac cAMP, ECC, and arrhythmia by phosphodiesterases - Abstract Autonomic dysregulation and aberrant intracellular signaling are hallmarks of both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Cyclic AMP (cAMP) is a key second messenger that transduces extracellular autonomic adrenergic signals to control downstream contractility and electrophysiology on a beat-to-beat basis. Aberrant cAMP signaling likely plays an important role in Ca2+ mishandling, contractile dysfunction, and arrhythmias in HF. cAMP is highly compartmentalized by b-adrenoceptor (b-AR)-induced cAMP synthesis and phosphodiesterase (PDE)-mediated degradation. The overall goal of this project is to determine the differential role of heterogeneous PDE4D signaling in contributing to dysfunctional excitation-contraction coupling (ECC) and arrhythmias in HFpEF vs. HFrEF in a sex-dependent manner. The main hypothesis that will be tested in this project is that either too much or too little PDE activity in cardiomyocytes can impair ECC and promote arrhythmias, and that underlying sex differences in PDE activity modulate sex-dependent responses. Using a novel integrated whole-heart imaging approach combined with single cell analysis and detailed subcellular signaling studies and FRET-based reporters, we will comprehensively determine signaling responses and functional outcomes from the molecular, cellular, to whole- heart level, which may ultimately suggest more personalized treatment strategies for men and women with HF.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $650,028 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cardiovascular Diseases Research	000	1	9/9/2025	NEW	$650,028
														Subtotal = $650,028

Grand Total All Awards = $650,028

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Sex-dependent regulation of cardiac cAMP, ECC, and arrhythmia by phosphodiesterases

Award Number: R01HL179122

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/09/2025

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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