Rescuing Cardiac Malfunction

Abstract

See related articles, pages 1473–1482 In response to various hypertrophic stimuli, the heart undergoes alterations in structure and function. One mechanism by which the heart adapts to physiological and pathological stimuli is an increase in size of individual cardiac myocytes, and when those stimuli are removed, the size of the myocytes can decrease. Modulation of cardiac size thus requires a very careful balance between protein synthesis and protein degradation, and any imbalance in these systems could be of potential damage to the heart. Increased protein synthesis in hypertrophied hearts is accompanied by “protein quality control” to eliminate aggregated unfolded proteins, but a failure of this monitoring system eventually leads to cardiac dysfunction.1 Heat shock proteins (HSPs) have chaperone-like properties that can bind to unfolded proteins and prevent their denaturation and aggregation.2 In recent genome surveys of mice, rats, and humans, small-molecular-weight heat shock proteins (sHSPs ≈15 to 30 kDa) have been identified. αB crystalline (CryAB) is a member of the sHSPs that is expressed at high levels in cardiomyocytes.2 CryAB has chaperone-like properties and also binds to both desmin and cytoplasmic actin which helps to maintain cytoskeletal integrity. Previous studies have shown that a mutation in CryAB mimics a form of desmin-related cardiomyopathy.3 Overexpressing CryAB in cultured cardiomyocytes and in transgenic mouse hearts protects against ischemia/reperfusion–induced cell death4,5; on the other hand, double knockout of the small heat shock proteins CryAB/SHSP2 induces abnormal cardiac growth and defective myocardial relaxation.6 In this issue of Circulation Research , Kumarapeli et al7 address and confirm the roles of CryAB in response to …