Structure and function of contractile proteins in human dilated cardiomyopathy.

The pathogenesis of reduced systolic left ventricular function in dilated cardiomyopathy is yet unclear. To analyze a possible involvement of contractile protein, function and structure of left ventricular myofibrils were examined in hearts of patients with advanced cardiomyopathy undergoing heart transplantation and in normal control hearts (from renal transplant donors). Myosin and actin content of the left ventricular myocardium was slightly reduced in cardiomyopathic hearts. Myofibrillar polypeptide composition was determined using two-dimensional electrophoresis and immunoblotting. No differences in constituting polypeptides were apparent, including Z-line proteins and proteins of the endosarcomeric lattice. M-line-bound creatine kinase was identical in both groups. Further, basal and maximal myofibrillar adenosine triphosphatase (ATPase) activities were unaltered in dilated cardiomyopathy. The structure of purified myosin was identical in both groups by the following criteria: electrophoretic mobility of native myosin, identical pattern of light chains after isoelectric focusing, identical cleavage peptides of myosin's heavy chain, and identical patterns after immunoblotting of heavy chain cleavage peptides using polyclonal antibodies generated against myosin from normal and cardiomyopathic ventricles. Ca2+-activated, K+-EDTA-activated and actin-activated myosin ATPase activities were identical in control and cardiomyopathic hearts. A structural alteration or functional defect of myofibrils does not seem to be primarily involved in the pathogenesis of reduced myocardial contractility in dilated cardiomyopathy.