Sudden cardiac death in the young: cytokines and pathways

Abstract

Objectives: The purpose of this paper is to clarify the cytokines and signaling pathways involved in the mechanisms of sudden cardiac death (SCD) in the young.

Methods: The representing literature concerning the cytokines and signaling pathways of SCD in the young were retrieved and analyzed.

Results: Extrinsic and intrinsic apoptotic pathways, influenced by growth factor pathways, may render arrythmogenic cardiac disorders and ultimately lead to SCD. Other cytokines probably involved in the mechanisms of SCDs in the young may include heme oxygenase-1 and the gaseous molecules (carbon monoxide and nitric oxide), insulin-like growth factor-1, gap junctional proteins and homeobox transcription factor NKX2-5, etc., which may be responsible for atrioventricular conduction impairments. Active therapeutics options for the pertinent arrhythmias have significantly reduced the incidence of SCD in the young.

Conclusions: The apoptotic and growth factor signaling pathways are the two major ways leading to conduction system impairment and eventual SCDs. The prophylactic antiarrhythmic agent, device therapies, or surgical operation could dramatically reduce SCD incidence. Good understanding of the mechanisms of the cytokine-related pathways is crucial for the treatment of the causative cardiac disorders responsible for SCDs in the young. New agents including apoptotic blockers, heme metabolite homologues, and c-Src, PIK3 and NKX2-5 inhibitors, etc., are anticipated for the prevention of SCDs in the near future.