Original Article Protein quality control in protection against systolic overload cardiomyopathy: the long term role of small heat shock proteins
Asangi R. K. Kumarapeli, Kathleen Horak, Xuejun Wang
Division of Basic Biomedical Sciences and Cardiovascular Research Institute, Sanford School of Medicine of the University of South Dakota, Vermillion, SD 57069, USA.
Received July 9, 2010; accepted July 20, 2010, available online July 21, 2010
Abstract: Molecular chaperones represent the first line of defense of intracellular protein quality control. As a major constituent of molecular chaperones, heat shock proteins (HSP) are known to confer cardiomyocyte short- term protection against various insults and injuries. Previously, we reported that the small HSP B-crystallin (CryAB) attenuates cardiac hypertrophic response in mice subjected to 2 weeks of severe pressure overload. However, the long-term role of small HSPs in cardiac hypertrophy and failure has rarely been studied. The present study investigates the cardiac responses to chronic severe pressure overload in CryAB/HSPB2 germ line ablated (KO) and cardiac-specific CryAB overexpressing transgenic (TG) mice. Pressure overload was induced by transverse aortic constriction in KO, TG, and non-transgenic wild type (NTG) control mice and 10 weeks later molecular, cellular, and whole organ level hypertrophic responses were analyzed. As we previously described, CryAB/HSPB2 KO mice showed abnormal baseline cardiac physiology that worsened into a restrictive cardiomyopathic phenotype with aging. Severe pressure overload in these mice led to rapid deterioration of heart function and development of congestive cardiac failure. Contrary to their short term protective phenotype, CryAB TG mice showed no significant effects on cardiac hypertrophic responses and very modest improvement of hemodynamics during chronic systolic overload. These findings indicate that small HSPs CryAB and/or HSPB2 are essential to maintain cardiac structure and function but overexpression of CryAB is not sufficient to confer a sustained protection against chronic systolic overload. (AJTR1007004).
Address all correspondence to: Xuejun Wang, MD, PhD Basic Biomedical Science Sanford School of Medicine University of South Dakota 414 E Clark Street, Vermillion SD 57069, USA. Tel: (605) 677-5132, Fax: (605)-677-6381 E-mail: Xuejun.Wang@usd.edu