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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 αB-crystallin (CryAB) attenuates cardiac hypertrophic response in mice subjected to 2 weeks of severe pressure overload. However, the longterm 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 cardiacspecific 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.

Original languageEnglish (US)
Pages (from-to)390-401
Number of pages12
JournalAmerican Journal of Translational Research
Volume2
Issue number4
StatePublished - Oct 8 2010

Fingerprint

Small Heat-Shock Proteins
Cardiomyopathies
Quality Control
Quality control
Pressure
Molecular Chaperones
Transgenic Mice
Proteins
Heart Failure
Phenotype
Crystallins
Physiology
Cardiomegaly
Hemodynamics
Heat-Shock Proteins
Cardiac Myocytes
Constriction
Germ Cells
Deterioration
Aging of materials

Keywords

  • Cardiac remodeling
  • Fetal genes
  • Hypertrophy
  • Pressure overload
  • Small heat shock protein

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

Cite this

Protein quality control in protection against systolic overload cardiomyopathy : The long term role of small heat shock proteins. / Kumarapeli, Asangi R.K.; Horak, Kathleen; Wang, Xuejun.

In: American Journal of Translational Research, Vol. 2, No. 4, 08.10.2010, p. 390-401.

Research output: Contribution to journalArticle

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