AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 2010;2(4):390-401

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).

Keywords: Small heat shock protein, pressure overload, hypertrophy, fetal genes, cardiac remodeling

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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