# Role of Endothelin-1 signaling in the development and progression of atrial fibrillation

> **NIH NIH K08** · NORTHWESTERN UNIVERSITY · 2023 · $163,080

## Abstract

SUMMARY Atrial fibrillation (AF) is the most common sustained arrhythmia. It is associated with significant
morbidity and mortality, being a leading cause of stroke. As age is a major risk factor for AF, this arrhythmia is
becoming an epidemic, with significant socioeconomic burden. Unfortunately, current therapies for AF are
suboptimal: pharmacologic therapies and catheter ablation have <50% efficacy, particularly in persistent AF. A
better understanding of the molecular mechanisms of AF will be crucial for the development of new therapies.
AF is a multifactorial disease, with chronic insults leading to progressive changes in the myocardium with
electrical, structural and autonomic remodeling. Endothelial dysfunction is a hallmark of most risk factors for AF
including heart failure, hypertension and diabetes. While multiple studies showed an association between
endothelial dysfunction and AF, the causal relationship remains unknown. Dr Pfenniger proposes to investigate
the role of endothelial dysfunction, and specifically of its major effector Endothelin-1, in AF using two clinically
relevant large animal models of AF, and harnessing novel gene therapy tools with high translational potential.
This proposal aims to first characterize the temporal and spatial relationship between endothelial dysfunction
and AF, with a particular focus on the transition from paroxysmal to persistent AF. In addition, this work will aim
to determine the mechanisms by which Endothelin-1 creates an AF substrate by promoting autonomic,
electrical and structural atrial remodeling. The objective of this proposal aligns closely with NHLBI's identified
strategic vision to investigate newly discovered pathobiological mechanisms important to the onset and
progression of heart, lung, blood, and sleep (HLBS) health. This Career Development Award will support Dr.
Pfenniger's transition to an independent physician-scientist. Dr. Pfenniger is currently an Assistant Professor at
Northwestern University, with the support of a KL2 Mentored Career Development Award and an AHA Career
Development Award. Dr. Pfenniger will carry out this work at the Feinberg Cardiovascular and Renal Research
Institute at Northwestern University under the primary mentorship of Dr. Rishi Arora. As a physician-scientist in
electrophysiology, Dr. Pfenniger will uniquely benefit from the support of her mentoring team led by Dr. Arora,
an internationally recognized physician-scientist with specialization in basic, translational and clinical
electrophysiology, who possesses expertise in large animal models of AF. The combination of mentors with
distinct expertise – EC coupling (Dr. Wasserstrom), high-throughput cellular electrophysiology (Dr. George),
vascular biology (Dr. Vaughan), translational AF research (Dr. Passman), advanced cardiovascular imaging
(Drs. Lee and Shah), and cardiovascular genetics (Dr. Roy-Puckelwartz) will allow Dr. Pfenniger to build on her
current skills and help her carve out her own n...

## Key facts

- **NIH application ID:** 10723916
- **Project number:** 1K08HL169904-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Anna Pfenniger
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $163,080
- **Award type:** 1
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10723916

## Citation

> US National Institutes of Health, RePORTER application 10723916, Role of Endothelin-1 signaling in the development and progression of atrial fibrillation (1K08HL169904-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10723916. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*