Myocardial Ischemia, Reperfusion Injury, Heat Shock Proteins and Chaperones

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Fig1: Tc99m Sestamibi Cardiac SPECT scan: reversible perfusion defect consistant with left anterior descending artery territory ischemia (arrows) Fig2: 3D conformational model of HSP 70 (source: imike.blogs.sapo.pt/ arquivo/hsp702.jpg)

Myocardial infarct and ischemia remain the number one cause of death in developed nations. Improved diagnosis and treatment have allowed the rapid reperfusion of myocardial tissue by surgical, interventional or pharmacological means, decreasing mortality and morbidity. Prolonged ischemia results in severe infarction and necrosis, reperfusion produces few beneficial effects and may contribute further to tissue reperfusion injury, including arrhythmia and myocardial stunning. Ischemic damage takes place in the absence of oxygen, whereas reperfusion damage is thought to be induced predominantly by oxygen-free radicals. The presence of oxygen-free radicals may contribute to calcium overload, protein malfolding, and partial protein denaturation leading to a decreased calcium binding and dysfunction of myofilament proteins. Myocardial protection against ischemia/reperfusion injury has been the subject of experimental and clinical research. In many animal species including humans, HSP (Heat Shock Proteins) 70/72 are upregulated during ischemia. During cardiac surgery the HSP induction is widely referred to as "ischemic preconditioning". The protective effect of HSP 70 against reperfusion injury and myocardial dysfunction can be explained with the known "chaperone" function of members of the HSP 70 family. Chaperones are proteins that bind to other proteins, facilitating proper protein folding, assembly, transport and translocation. They are highly conserved and could play a role in buffering mutations that could otherwise cause protein malfolding. In that role they could be important for evolution and biodiversity.

Source: Protection Against Myocardial Dysfunction After a Brief Ischemic Period in Transgenic Mice Expressing Inducible Heat Shock Protein 70 Susanne U. Trost, Jeffrey H. Omens, William J. Karlon, Markus Meyer, Ruben Mestril, James W. Covell, and Wolfgang H. Dillmann Division of Endocrinology & Metabolism, and Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla, California 92093-0618. J. Clin. Invest. Vol 101. No 4. Feb 1998 855-862