The Stress-Response MAP Kinase Signaling in Cardiac Arrhythmias

Abstract

Stress-response kinases, the mitogen-activated protein kinases (MAPKs) are activated in response to the challenge of a myriad of stressors. c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERKs), and p38 MAPKs are the predominant members of the MAPK family in the heart. Extensive studies have revealed critical roles of activated MAPKs in the processes of cardiac injury and heart failure and many other cardiovascular diseases. Recently, emerging evidence suggests that MAPKs also promote the development of cardiac arrhythmias. Thus, understanding the functional impact of MAPKs in the heart could shed new light on the development of novel therapeutic approaches to improve cardiac function and prevent arrhythmia development in the patients. This review will summarize the recent findings on the role of MAPKs in cardiac remodeling and arrhythmia development and point to the critical need of future studies to further elucidate the fundamental mechanisms of MAPK activation and arrhythmia development in the heart.

Association of Complement and MAPK Activation With SARS-CoV-2–Associated Myocardial Inflammation

“…Signals from pathogen-associated molecular patterns (including viral infections) and other extracellular cues are transmitted into the cell and amplified by MAPK and have been implicated in the pathophysiologic mechanisms of various inflammatory diseases, including cardiac injury. Inhibition of MAPK-associated pathways has been associated with reductions in fibrosis and improvements in heart function in animal models of myocardial injury, offering therapeutic approaches to cardiac inflammation …”

Transcriptional regulation of stress kinase JNK2 in pro-arrhythmic CaMKIIδ expression in the aged atrium

“…JNK, originally identified as a stress protein kinase, is activated in response to a variety of extrinsic and intrinsic stresses. 2,36 During the aging process, cardiomyocytes undergo various cellular changes such as enhanced oxidative stress as well as accumulating other chemical or biophysical stresses in the heart. 37,38 Although JNK may be activated with increasing age as the stresses accumulate, 6,39 our current and previous results suggest that activated atrial JNK is a consistent feature of aged atrium among different species (humans, rabbits, and mice).…”

Stress Signaling JNK2 Crosstalk With CaMKII Underlies Enhanced Atrial Arrhythmogenesis

“…c-Jun N-terminal kinase (JNK) is a well-characterized stress-response kinase that is activated in response to various cellular stresses such as UV light, ischemia, inflammatory cytokines, and aging. 5-9 Interestingly, many of these stresses are also well-established cardiovascular risk factors and JNK activation has been observed in cardiovascular conditions like ischemia, hypertrophy and HF. All these conditions are associated with increased AF risk.…”