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J Thorac Cardiovasc Surg 2007;134:1461-1470
© 2007 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Phosphorylation and translocation of heat shock protein 27 and B-crystallin in human myocardium after cardioplegia and cardiopulmonary bypass

Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.

Received for publication February 13, 2007; revisions received June 14, 2007; accepted for publication June 22, 2007.

^_* Address for reprints: Frank W. Sellke, MD, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, LMOB 2A, 110 Francis St, Boston, MA 02215. (Email: fsellke{at}caregroup.harvard.edu).

Objectives: Cardiac surgery using cardioplegia and cardiopulmonary bypass subjects myocardium to hypothermic reversible ischemic injury that can impair cardiac function. Research in animal and cell models demonstrates that acute myocardial ischemia/reperfusion injury causes phosphorylation of heat shock protein 27 and B-crystallin. Phosphorylation of heat shock protein 27 and B-crystallin is implicated in the regulation of both beneficial and detrimental responses to ischemic injury. The phosphorylation status of these proteins in human myocardium after ischemic insults associated with cardioplegia and cardiopulmonary bypass is unknown.

Methods: Right atrial appendage and chest wall skeletal muscle samples were collected from patients before and after cardioplegia and cardiopulmonary bypass. Cardioplegia and cardiopulmonary bypass-induced changes in phosphorylation and localization of heat shock protein 27 and B-crystallin were determined using immunoblot and confocal microscopy with total and phospho-specific antibodies.

Results: Cardioplegia and cardiopulmonary bypass increased the phosphorylation of heat shock protein 27 on serine 15, 78, and 82, and B-crystallin on serine 59 and 45, but not serine 19. The majority of heat shock protein 27 and B-crystallin localized to I-bands of cardiac myofilaments and shifted to a detergent insoluble fraction after cardioplegia and cardiopulmonary bypass. Cardioplegia and cardiopulmonary bypass–induced phosphorylation of specific heat shock protein 27 and B-crystallin residues were associated with additional subcellular locations. Increases in phosphorylation of heat shock protein 27 and B-crystallin were negatively correlated with cardiac function after surgery.

Conclusion: Cardiac surgery using cardioplegia and cardiopulmonary bypass is associated with phosphorylation and myofilament translocation of heat shock protein 27 and B-crystallin in human myocardium. Phosphorylation of specific heat shock protein 27 and B-crystallin serine residues is associated with distinct localization. Understanding the human myocardial small heat shock protein response may have significant implications for surgical myocardial protection.