# Atrial and blood JNK in Postoperative AF

> **NIH HL R01** · OHIO STATE UNIVERSITY · 2026 · $670,980

## Abstract

Atrial fibrillation (AF) is the most common arrhythmia and has a high risk of mortality and morbidities. Among the
general AF population, new-onset postoperative atrial fibrillation (POAF) is the most common complication after open-
heart surgery, which significantly increased mortality and amplifies hospital and patient costs. The mechanisms
underlying POAF are unclear, thus effective prediction and/or prevention remain unavailable. This proposal aims to
fill this knowledge gap by identifying stress-response kinase JNK as a novel POAF biomarker for surgery patients
and exploring the translational potential of local JNK inhibition in atria as a novel anti-POAF therapeutic
approach. Predisposing factors for POAF include advanced age, binge alcohol, as well as intraoperative and
postoperative atrial injury and/or ischemia. One common element among these factors is tremendously increased
cellular stress, which is known to activate the c-Jun N-terminal kinases (JNKs), an important stress-response kinase.
We recently discovered and reported a previously unrecognized causal link between cardiac JNK activation and
abnormal cell-cell communication (via gap junction channels) as well as abnormal Ca triggered activities which
enhance AF propensity. Our intriguing preliminary findings suggest that atrial JNK activation is well correlated to
POAF incidence in patients within 10 days of coronary artery bypass graft (CABG) surgery, indicating POAF likely
involves JNK activation and possible JNK-driven atrial arrhythmogenesis. Intriguingly, our preliminary results show
for the first time that JNK is present in blood. And JNK activation in the heart increases blood JNK. Accordingly, the
concordant atrial JNK activation and rise in plasma JNK levels correlates nicely to the increased incidence of AF.
Next, we found that most of the plasma JNKs are carried by microparticles (MPs) circulating in the blood. Our pilot
data further suggest that heart cells shed JNK-microparticles (JNK-MP

## Key facts

- **NIH application ID:** 11264773
- **Project number:** 5R01HL168728-10
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Xun  Ai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $670,980
- **Award type:** 5
- **Project period:** 2023-04-14T00:00:00 → 2028-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11264773

## Citation

> US National Institutes of Health, RePORTER application 11264773, Atrial and blood JNK in Postoperative AF (5R01HL168728-10). Retrieved via AI Analytics 2026-05-19 from https://api.ai-analytics.org/grant/nih/11264773. Licensed CC0.

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