STRESS PROTEIN 60 DURING MYOCARDIAL ISCHEMIA

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Coronary artery disease can lead to chronic heart failure, need for revascularization (by-pass surgery), or life-threatening cardiac arrhythmias. It is the cause of one and a half million acute myocardial infarctions per year in the USA, more than half of them lethal. Its cost is the highest of all Current medical diseases in the nation. Coronary artery disease affects the blood supply of the heart muscle (myocardium) and, therefore, decreases oxygen delivery to myocardial cells. The mitochondria of cardiac myocytes is one of the major targets for ischemia- induced damage. Limitations of oxygen delivery reduces mitochondrial oxidative phosphorylation and contributes to the reduction of intracellular ATP levels. Some investigators have indicated that the inability of the mitochondria to self-repair following restoration of blood flow may be one of the crucial events leading to the ultimate death of myocardial cells. Although it is not clear if sarcolemmal or mitochondrial damage is the main event in the irreversible damage of the myocardial cell, the role of mitochondrial changes in decreased myocardial functions are not questioned. Recent studies have shown that heat shock protein (HSP) 60, which is a member of the stress protein family and are thought to have a protective role during oxidative stress, is required for the assembly of multimeric enzyme complexes within the mitochondria. We have recently found that during acute occlusion of the descending coronary artery for 30 minutes in the rat heart, which leads to ischemia in the left ventricle, there is a marked and specific increase in HSP6O mRNA level. This finding leads us to believe that HSP6O as other related HSPs may have a protective role and is probably involved in the repair of the mitochondrial enzymatic complexes vital for the normal function of the mitochondria. It is our objective to investigate this ischemia-induced change in HSP6O expression and determine if HSP60 mediates protection processes in the mitochondria that contribute to recovery from ischemic injury in the myocardial cell.