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1 Molecular & Cellular Cardiology, University of California, Davis, Davis, California, United States
2 Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Bonn, Germany
3 Department of Biomedical Engineering, University of California, Davis, Davis, California, United States
4 Cardiology, Methodist Hospital, Houston, Texas, United States
5 Molecular & Cellular Cardiology, University of California, Davis, Davis, California, United States; Medical Pharmacology, University of California, Davis, Davis, California, United States; Cardiology, VA Medical Center, Sacramento, California, United States
* To whom correspondence should be addressed. E-mail: aaknowlton{at}ucdavis.edu.
Background -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 are unchanged. Furthermore, we observed that acute injury in adult cardiac myocytes results 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 provides a pathway for cardiac injury. Methods and Results - 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 localizes to the plasma membrane and is also found in the plasma early in heart failure. Plasma membrane HSP60 localized to lipid rafts, and was detectable on the cell surface by both flow cytometry and confocal microscopy. Localization of HSP60 to the cell surface correlated with increased apoptosis. Conclusions - 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 pro-inflammatory state, including an increase in TNF-
. Thus, abnormal trafficking of HSP60 to the cell surface may be an early trigger for myocyte loss and the progression of heart failure.
This article has been cited by other articles:
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  J. E. Fildes, S. M. Shaw, N. Yonan, and S. G. Williams The Immune System and Chronic Heart Failure: Is the Heart in Control? J. Am. Coll. Cardiol., March 24, 2009; 53(12): 1013 - 1020. [Abstract] [Full Text] [PDF]
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 B. J.J.M. Brundel, L. Ke, A.-J. Dijkhuis, X. Qi, A. Shiroshita-Takeshita, S. Nattel, R. H. Henning, and H. H. Kampinga Heat shock proteins as molecular targets for intervention in atrial fibrillation Cardiovasc Res, June 1, 2008; 78(3): 422 - 428. [Abstract] [Full Text] [PDF]
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