Sudden cardiac death in the young: Cytokines and pathways

Abstract

Background and Purpose: The underlying mechanisms of sudden cardiac death in terms of cytokines and pertinent signaling pathways have not been previously elaborated. The purpose of this paper is to clarify the cytokines and signaling pathways involved in the mechanisms of sudden cardiac death in the young. Materials and Methods: Medical literature of sudden cardiac death in the young of recent decades were carefully collected as studying materials, and comprehensively reviewed and analyzed. Results: Extrinsic and intrinsic apoptotic pathways, influenced by growth factor pathways, may render arrythmogenic cardiac disorders and ultimately lead to sudden cardiac death. Other cytokines probably involved in the mechanisms of sudden cardiac death 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, which may be responsible for atrioventricular conduction impairments. Active therapeutic options for the pertinent arrhythmias have significantly reduced the incidence of sudden cardiac death in the young. The apoptotic and growth factor signaling pathways are the two major ways leading to conduction system impairment and eventual sudden cardiac death. Conclusions: The prophylactic antiarrhythmic agent, device therapies, or surgical operation could dramatically reduce sudden cardiac death incidence. Good understanding of the mechanisms of the cytokine-related pathways is crucial for the treatment of the causative cardiac disorders responsible for sudden cardiac death 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 sudden cardiac death in the near future.