Contractile protein transitions in human cardiac overload: reality and limitations.
Attention has focused on possible defects at the level of the contractile proteins in myocardial hypertrophy and failure. In small mammals such as the rat and rabbit, myofibrillar and myosin ATPases are depressed in situations of decreased contractility. Converse increases in enzymic activity together with enhanced contractility are seen in the hyperthyroid state. The molecular basis for these changes in enzymic activity is now known to result from transitions in three heavy chain isoenzymes of myosin, V1, V2 and V3 which possess different ATPase activities. Transitions in isoenzyme composition occur during hypertrophy, thyrotoxicosis and development in the myocardium of small mammals. In larger animals such as the rhesus monkey, baboon, cow and in particular, man, only V3, the lowest ATPase isoenzyme can be detected in the normal ventricle and this is the only form present throughout development. Confirmation of the lack of developmental transitions in myosin heavy chains expressed in man is also obtained by sensitive peptide mapping techniques. Changes in myosin heavy chain isoenzymes in large mammals as an explanation of depressed contractile function cannot therefore be made on the presently available evidence. Indeed, evidence for lowered ATPase activities in the failing human myocardium is equivocal. Evidence is however provided for transitions in light chain isoenzymes of myosin in situations of cardiac overload. Caution should be exercised in using small animals as models of myocardial hypertrophy and failure in man.
D000251:Adenosine Triphosphatases / Q000032:analysis*; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology*; D002417:Cattle; D004586:Electrophoresis; D006801:Humans; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000032:analysis*; D008253:Macaca mulatta; D009206:Myocardium / Q000201:enzymology*; D009210:Myofibrils / Q000201:enzymology; D009218:Myosins / Q000032:analysis*; D010215:Papio; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
D007527:Isoenzymes; D000251:Adenosine Triphosphatases; D009218:Myosins