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, A. A. Knowlton

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


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)
Pages (from-to)H2238-H2247
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4
StatePublished - Oct 2007


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

ASJC Scopus subject areas

  • Physiology


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