HSP60 in heart failure: Abnormal distribution and role in cardiac myocyte apoptosis

Li Lin, S. C. Kim, Yin Wang, S. Gupta, B. Davis, S. I. Simon, G. Torre-Amione, Anne A Knowlton

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Heat shock protein (HSP) 60 is a mitochondrial and cytosolic protein. Previously, we reported that HSP60 doubled in end-stage heart failure, even though levels of the protective HSP72 were unchanged. Furthermore, we observed that acute injury in adult cardiac myocytes resulted in movement of HSP60 to the plasma membrane. We hypothesized that the inflammatory state of heart failure would cause translocation of HSP60 to the plasma membrane and that this would provide a pathway for cardiac injury. Two models were used to test this hypothesis: 1) a rat model of heart failure and 2) human explanted failing hearts. We found that HSP60 localized to the plasma membrane and was also found in the plasma early in heart failure. Plasma membrane HSP60 localized to lipid rafts and was detectable on the cell surface with the use of both flow cytometry and confocal microscopy. Localization of HSP60 to the cell surface correlated with increased apoptosis. In heart failure, HSP60 is in the plasma membrane fraction, on the cell surface, and in the plasma. Membrane HSP60 correlated with increased apoptosis. Release of HSP60 may activate the innate immune system, promoting a proinflammatory state, including an increase in TNF-α. Thus abnormal trafficking of HSP60 to the cell surface may be an early trigger for myocyte loss and the progression of heart failure.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 2007

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Cardiac Myocytes
Heart Failure
Apoptosis
Cell Membrane
Chaperonin 60
Mitochondrial Proteins
Wounds and Injuries
Confocal Microscopy
Muscle Cells
Immune System
Flow Cytometry
Lipids
Membranes

Keywords

  • Cytokines
  • Heat shock proteins
  • Plasma membrane
  • Protein trafficking

ASJC Scopus subject areas

  • Physiology

Cite this

HSP60 in heart failure : Abnormal distribution and role in cardiac myocyte apoptosis. / Lin, Li; Kim, S. C.; Wang, Yin; Gupta, S.; Davis, B.; Simon, S. I.; Torre-Amione, G.; Knowlton, Anne A.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 293, No. 4, 10.2007.

Research output: Contribution to journalArticle

Lin, Li ; Kim, S. C. ; Wang, Yin ; Gupta, S. ; Davis, B. ; Simon, S. I. ; Torre-Amione, G. ; Knowlton, Anne A. / HSP60 in heart failure : Abnormal distribution and role in cardiac myocyte apoptosis. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 293, No. 4.
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