αb-crystallin suppresses pressure overload cardiac hypertrophy

Asangi R.K. Kumarapeli, Huabo Su, Wei Huang, Mingxin Tang, Hanqiao Zheng, Kathleen M. Horak, Manxiang Li, Xuejun Wang

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

αB-Crystallin (CryAB) is the most abundant small heat shock protein (HSP) constitutively expressed in cardiomyocytes. Gain- and loss-of-function studies demonstrated that CryAB can protect against myocardial ischemia/reperfusion injury. However, the role of CryAB or any HSPs in cardiac responses to mechanical overload is unknown. This study addresses this issue. Nontransgenic mice and mice with cardiomyocyte-restricted transgenic overexpression of CryAB or with germ-line ablation of the CryAB/HSPB2 genes were subjected to transverse aortic constriction or sham surgery. Two weeks later, cardiac responses were analyzed by fetal gene expression profiling, cardiac function analyses, and morphometry. Comparison among the 3 sham surgery groups reveals that CryAB overexpression is benign, whereas the knockout is detrimental to the heart as reflected by cardiac hypertrophy and malfunction at 10 weeks of age. Compared to nontransgenic mice, transgenic mouse hearts showed significantly reduced NFAT transactivation and attenuated cardiac hypertrophic responses to transverse aortic constriction but unchanged cardiac function, whereas NFAT transactivation was significantly increased in cardiac and skeletal muscle of the knockout mice at baseline, and they developed cardiac insufficiency at 2 weeks after transverse aortic constriction. CryAB overexpression in cultured neonatal rat cardiomyocytes significantly attenuated adrenergic stimulation-induced NFAT transactivation and hypertrophic growth. We conclude that CryAB suppresses cardiac hypertrophic responses likely through attenuating NFAT signaling and that CryAB and/or HSPB2 are essential for normal cardiac function.

Original languageEnglish (US)
Pages (from-to)1473-1482
Number of pages10
JournalCirculation research
Volume103
Issue number12
DOIs
StatePublished - Dec 5 2008

Fingerprint

Crystallins
Cardiomegaly
Cardiac Myocytes
Constriction
Transcriptional Activation
Pressure
Small Heat-Shock Proteins
Myocardial Reperfusion Injury
Gene Expression Profiling
Reperfusion Injury
Knockout Mice
Germ Cells
Adrenergic Agents
Transgenic Mice
Myocardial Ischemia
Myocardium
Skeletal Muscle
Growth
Genes

Keywords

  • Heat shock proteins
  • Hypertrophy
  • Myocyte-enriched
  • Nuclear factors of activated T cells (NFAT)

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Kumarapeli, A. R. K., Su, H., Huang, W., Tang, M., Zheng, H., Horak, K. M., ... Wang, X. (2008). αb-crystallin suppresses pressure overload cardiac hypertrophy. Circulation research, 103(12), 1473-1482. https://doi.org/10.1161/CIRCRESAHA.108.180117

αb-crystallin suppresses pressure overload cardiac hypertrophy. / Kumarapeli, Asangi R.K.; Su, Huabo; Huang, Wei; Tang, Mingxin; Zheng, Hanqiao; Horak, Kathleen M.; Li, Manxiang; Wang, Xuejun.

In: Circulation research, Vol. 103, No. 12, 05.12.2008, p. 1473-1482.

Research output: Contribution to journalArticle

Kumarapeli, ARK, Su, H, Huang, W, Tang, M, Zheng, H, Horak, KM, Li, M & Wang, X 2008, 'αb-crystallin suppresses pressure overload cardiac hypertrophy', Circulation research, vol. 103, no. 12, pp. 1473-1482. https://doi.org/10.1161/CIRCRESAHA.108.180117
Kumarapeli ARK, Su H, Huang W, Tang M, Zheng H, Horak KM et al. αb-crystallin suppresses pressure overload cardiac hypertrophy. Circulation research. 2008 Dec 5;103(12):1473-1482. https://doi.org/10.1161/CIRCRESAHA.108.180117
Kumarapeli, Asangi R.K. ; Su, Huabo ; Huang, Wei ; Tang, Mingxin ; Zheng, Hanqiao ; Horak, Kathleen M. ; Li, Manxiang ; Wang, Xuejun. / αb-crystallin suppresses pressure overload cardiac hypertrophy. In: Circulation research. 2008 ; Vol. 103, No. 12. pp. 1473-1482.
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