Cardiac myofilament function in human heart failure and diabetes.

摘要

Heart failure is a malady of epidemic proportions in the United States. Diabetes is also a common illness and is one of the causes of cardiomyopathy in humans. The role of cardiac myofilament function in the pathophysiology of human cardiomyopathy is not well understood.; Two studies were performed using human myocardium to determine the role of myofilament function in end-stage idiopathic dilated cardiomyopathy (IDCM) and in diabetic cardiomyopathy. Skinned myocyte mechanical experiments were conducted to determine the maximum force, cooperativity of calcium binding to troponin I, and the calcium sensitivity of troponin in both study groups and controls. Biochemical analyses were also performed to determine the phosphorylation level of troponin I and T. A third study was conducted to determine the effects of freezing human tissue, for tissue preservation, on the accuracy of our mechanical measurements.; The findings revealed that cardiac myofilament calcium sensitivity was significantly decreased in human diabetes compared to controls. Conversely, we found no significant differences in myofilament function in end-stage idiopathic dilated cardiomyopathy. However, in one failure subset, we found that calcium response and maximum force improved with phosphatase treatment. Phosphorylation of TnI and TnT is increased in diabetes and may also play a role in IDCM. Finally, flash-freezing human myocardium did not alter the fidelity of these experiments.