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The role of stretch-activated Piezo1 channel in heart failure-associated atrial fibrillation

Award Number: R01HL178599
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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The role of stretch-activated Piezo1 channel in heart failure-associated atrial fibrillation - PROJECT SUMMARY Atrial fibrillation (AF) is the most common arrhythmia and a public health burden. One of the most significant risk factors for AF is heart failure (HF). AF and HF often coexist, exacerbate each other, and are associated with worse clinical outcomes, representing a common clinical conundrum. Atrial enlargement is universally observed in HF patients and previous studies have demonstrated that atrial stretch directly promotes arrhythmia. However, the underlying molecular mechanisms remain unclear. Our preliminary data revealed that the mechanosensitive channel Piezo1 is expressed in atrial cardiomyocytes and contributes to stretch-induced downstream changes. Therefore, we hypothesize that atrial stretch-induced Piezo1 activation contributes to atrial remodeling and AF predisposition in HF. In Aim1, we will use both in vitro and in vivo approaches to test the hypothesis that Piezo1 activation leads to pathological atrial remodeling, thus predisposing to AF. Our preliminary data suggested that Piezo1 activation, either pharmacologically or by mechanical stretch, directly promotes atrial hypertrophy and calcium mishandling, which are key properties of AF. In Aim2, we will elucidate the atrial-specific Piezo1 downstream pathways. In addition to focusing on calcium-associated signaling pathways, we will also perform unbiased -omics studies to identify novel atrial-specific Piezo1 downstream targets. In Aim3, we will test the therapeutic effect of blocking Piezo1 in HF-associated AF by both genetic and pharmacological approaches. The proposed studies will elucidate the roles of the stretch-activated Piezo1 channel and its downstream signaling pathways in HF-associated atrial remodeling and arrhythmogenesis. Our studies will uncover critical mechanisms in atrial stretch-associated pathophysiology and facilitate the development of novel anti-AF therapies.


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: 2026 ( Subtotal = $608,173 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Cardiovascular Diseases Research	000	1	6/30/2026	NEW	$608,173
														Subtotal = $608,173

Grand Total All Awards = $608,173

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The role of stretch-activated Piezo1 channel in heart failure-associated atrial fibrillation

Award Number: R01HL178599

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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