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Contractile protein transitions in human cardiac overload: Reality and limitations
36 CONTRACTILE
PROTEIN TRANSITIONS IN HUMAN CARDIAC OVERLOAD: REALITY AND LIMITATIONS. P. Cummins
Molecular
Cardiology Unit, Department of Cardiovascular Medicine University of Birmingham, Birmingham, B15 2TH, U.K.
Abnormalities in contractile protein function have long been proposed as a factor associated with the development of cardiac pressure and volume overload and subsequent hypertrophy. However, the relationship between primary causes and possible secondary, compensatory responses is far from clear. Moreover, the evidence to date has failed to demonstrate the presence of any disease specific, contractile protein gene products in situations where contractile performance is either markedly depressed or elevated. Nevertheless, myofibrillar function, as reflected in actomyosin ATPase activities clearly correlates with changes in contractility in a number of experimental cardiac pathologies. The underlying factors responsible for these activity changes are now known to result from differential expression of myosin isoenzyme populations that possess different heavy chain subunits (Hoh et al., (1979) FEBS Lett. 97, 330; Lompre et al., (1979) Nature 282, 105). The myosin isoenzymes characterised to date are all expressed at some stage during the normal developmental and adult lifespan but the relative proportions change markedly during conditions such as cardiac overload. Although these transitions are well documented in the ventricular myocardium of small animals such as the rat and rabbit, little is known as to whether similar changes occur in larger mammals, including man. The atria1 and ventricular myocardium of the bovine, rhesus monkey, baboon and human myocardium have therefore been investigated initially to establish the normal developmental and adult pattern of myosin isoenzyme populations. Both the heavy and light chain subunit isomorphs have been studied using a variety of sensitive analytical electrophoretic techniques. In the presence of pyrophosphate buffer, conditions which clearly resolve the V V and V myosin heavy chain isoenzymes in smaller mammalian ven%Licfes, on!?y one V type of isoenzyme was present in larger mammalian ventricles (Lam 2 ert, Janes and Cummins, in press). Similar results were obtained at all developmental stages from mid-foetal gestation to late adult life. The apparent absence of any heavy chain isoenzymes of myosin was confirmed using sensitive peptide mapping techniques. Atria1 myocardium however consistently displayed two types of isoenzyme in the adult, using pyrophosphate buffer. One of these comigrated with the ventricular form. No evidence of heavy chain isoenzyme transitions was obtained in the ventricular myocardium which could be used as a basis for explaining contractile changes during cardiac overload. Marked evidence for myosin light chain isoenzyme transitions was obtained both in the atria and ventricle, however, and the possible relationship of these to changes in cardiac pressure ---Al--L___i77 L^ Ai-- ..^_^ -I
PROTEIN TRANSITIONS IN HUMAN CARDIAC OVERLOAD: REALITY AND LIMITATIONS. P. Cummins
Molecular
Cardiology Unit, Department of Cardiovascular Medicine University of Birmingham, Birmingham, B15 2TH, U.K.
Abnormalities in contractile protein function have long been proposed as a factor associated with the development of cardiac pressure and volume overload and subsequent hypertrophy. However, the relationship between primary causes and possible secondary, compensatory responses is far from clear. Moreover, the evidence to date has failed to demonstrate the presence of any disease specific, contractile protein gene products in situations where contractile performance is either markedly depressed or elevated. Nevertheless, myofibrillar function, as reflected in actomyosin ATPase activities clearly correlates with changes in contractility in a number of experimental cardiac pathologies. The underlying factors responsible for these activity changes are now known to result from differential expression of myosin isoenzyme populations that possess different heavy chain subunits (Hoh et al., (1979) FEBS Lett. 97, 330; Lompre et al., (1979) Nature 282, 105). The myosin isoenzymes characterised to date are all expressed at some stage during the normal developmental and adult lifespan but the relative proportions change markedly during conditions such as cardiac overload. Although these transitions are well documented in the ventricular myocardium of small animals such as the rat and rabbit, little is known as to whether similar changes occur in larger mammals, including man. The atria1 and ventricular myocardium of the bovine, rhesus monkey, baboon and human myocardium have therefore been investigated initially to establish the normal developmental and adult pattern of myosin isoenzyme populations. Both the heavy and light chain subunit isomorphs have been studied using a variety of sensitive analytical electrophoretic techniques. In the presence of pyrophosphate buffer, conditions which clearly resolve the V V and V myosin heavy chain isoenzymes in smaller mammalian ven%Licfes, on!?y one V type of isoenzyme was present in larger mammalian ventricles (Lam 2 ert, Janes and Cummins, in press). Similar results were obtained at all developmental stages from mid-foetal gestation to late adult life. The apparent absence of any heavy chain isoenzymes of myosin was confirmed using sensitive peptide mapping techniques. Atria1 myocardium however consistently displayed two types of isoenzyme in the adult, using pyrophosphate buffer. One of these comigrated with the ventricular form. No evidence of heavy chain isoenzyme transitions was obtained in the ventricular myocardium which could be used as a basis for explaining contractile changes during cardiac overload. Marked evidence for myosin light chain isoenzyme transitions was obtained both in the atria and ventricle, however, and the possible relationship of these to changes in cardiac pressure ---Al--L___i77 L^ Ai-- ..^_^ -I