Basic/Translational Science -> Intact Heart Electrophysiology (includes Pharmacology and Optical Mapping) D-MP01 - Insights into novel genes, biomarkers and radioablation in arrhythmias (ID 31) Moderated ePoster

D-MP01-03 - The Stress-Response Kinase JNK: A Novel Biomarker For Post-Operative AF (ID 1485)

Disclosure
 J. Yan: Nothing relevant to disclose.

Abstract

Background: Among the general AF population, new-onset post-operative AF (POAF) is the most common complication after open-chest surgeries. POAF yields poor surgical outcomes and high mortality. To date, effective biomarkers for POAF prediction remain unavailable. Our group recently discovered a previously unrecognized causal link between a stress-response kinase JNK and AF risk in both humans and animal models.
Objective: Our goal was to test whether JNK is an AF biomarker for early AF interventions.
Methods: Various variables (age, BMI, HTN, β-blocker usage) was analyzed as POAF independent risk factors from coronary artery bypass graft surgery (CABG) patients using the multivariable logistic regression model. The link between atrial/plasma JNK and AF risk was assessed using biochemical assays and electrophysiological assessments in human organ donors and JNK transgenic (Tg) mice.
Results: Increasing age and high BMI were found to be independent POAF risk factors for CABG patients, while β-blocker use and HTN were not. In surgically removed atrial specimens from aged POAF and age-matched non-POAF CABG patients (normal BMI, no history of AF prior to surgery, preserved cardiac function and no history of major CVDs), significantly activated atrial JNK was well correlated to the POAF incidence, while non-POAF atria had a much lower level of JNK activation. This suggests a strong link between atrial JNK activation and POAF in aged CABG patients in the absence of other confounding POAF risk factors. In human organ donors, increasing age and high BMI were both linked to activated atrial JNK and enhanced AF susceptibility ex vivo. Interestingly, we discovered, for the first time, that JNK is present in the blood. And, plasma JNK is positively correlated with atrial JNK activity and AF inducibility in both aged and high BMI humans. In Tg JNK mice, activating heart-only JNK substantially increased plasma JNK and AF inducibility. Further, heart-only JNK inhibition (genetically) abolished the plasma JNK elevation and AF inducibility. These demonstrate a causal link between atrial JNK and plasma JNK and AF risk.
Conclusion: Our exciting findings strongly suggest atrial/plasma JNK could be a novel AF biomarker for early anti-AF intervention and a promising therapeutic target of AF.
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