Endoplasmic reticulum proteins in cardiac development and dysfunction.

An understanding of cardiac pathologies and the molecular mechanisms thereof is essential for the development of therapies for cardiovascular disease, a common cause of death in Western societies. Investigations into heart diseases have shown that the endoplasmic reticulum and its diverse functions may lie at the center of many cardiac pathologies. Animal models have demonstrated that in numerous cases, faulty endoplasmic reticulum activity is manifested in defective cardiogenesis or impaired heart function. These findings suggest that the endoplasmic and sarcoplasmic reticulum membranes may represent functionally independent organelles responsible for specialized functions in the heart. This review addresses the molecular pathways linking endoplasmic reticulum function and malfunction with impaired cardiac phenotypes. The endoplasmic reticulum affects cardiac development and function through Ca2+-dependent pathways, its catalytic role in the proper folding and targeting of membrane-bound and secretory proteins, and its response to cellular stress events, particularly hypoxic conditions. These pathways present potential novel targets for treatment of cardiac disease.