Structural and functional diversity of human ventricular myosin.
The role of subcellular alterations in the process of heart failure remains ill-defined. Because contractile performance of failing heart muscle is depressed, possible alterations in the myosin molecule could be of particular relevance. There is increasing evidence that myofibrillar ATPase activity is reduced in congestive heart failure, whereas the findings on myosin ATPase are still controversial. The molecular causes of the reduced activity are currently not known. Because alpha-MHC is present only in small amounts in normal ventricles, a shift in favor of beta-MHC is of minor importance. Also immunohistochemical data on subspecies of beta-MHC seem not to provide an explanation. A new type of myosin heterogeneity was found by optimizing native polyacrylamide gel electrophoresis in the presence of pyrophosphate. Two bands (VA and VB) were observed in ventricles of patients with valvular disease. Because the two bands were detected also in normal hearts of large mammals, the existence of VA/VB cannot be diagnostic of diseased heart. However, the VA/VB ratio was influenced by the hemodynamic load, whereby the fast migrating band (VA) increased with the diastolic and systolic load. Because a relationship with the hemodynamic load was observed only in surgical muscle specimens, it appears that this heterogeneity is prone to post mortem modification. Further work is required to identify the molecular nature of this heterogeneity and to examine the therapeutic potential of a pharmacological modification of the VA/VB ratio.
Rupp
H
H
Institute of Physiology II, University of Tübingen, FRG.
Jacob
R
R
D000328:Adult; D003971:Diastole; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D006333:Heart Failure / Q000378:metabolism*; D006349:Heart Valve Diseases / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008875:Middle Aged; D009218:Myosins / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry*; D013599:Systole
D007527:Isoenzymes; D009218:Myosins