title: Reduced myocardial sarcoplasmic reticulum Ca(2+)-ATPase protein expression in compensated primary and secondary human cardiac hypertrophy.
abstract: Pathological intracellular calcium handling has been proposed to underlie the alterations of contractile behavior in hypertrophied myocardium. However, the myocardial protein expression of intracellular calcium transport proteins in compensated human left ventricular hypertrophy has not yet been studied. We investigated septal myocardial specimens of patients suffering from hypertrophic obstructive cardiomyopathy (n=14) or from acquired aortic valve stenosis (n=11) undergoing myectomy or aortic valve replacement, respectively. For comparison, we studied non-hypertrophied myocardium of six non-failing hearts which could not be transplanted for technical reasons. The myocardial density of the calcium release channel of the sarcoplasmic reticulum (SR) was determined by(3)H-ryanodine binding. Myocardial contents of SR Ca(2+)-ATPase, phospholamban, calsequestrin and Na(+)/Ca(2+)-exchanger were analysed by Western blot analysis. The myocardial SR calcium release channel density was not significantly different in hypertrophied and non-failing human myocardium. In both hypertrophic obstructive cardiomyopathy and in aortic valve stenosis, SR Ca(2+)-ATPase expression was reduced by about 30% compared to non-failing myocardium (P<0.05), whereas the expression of phospholamban, calsequestrin, and the Na(+)/Ca(2+)-exchanger was unchanged. The decrease of SR Ca(2+)-ATPase expression was still observable when related to its regulatory protein phospholamban or to the myosin content of the homogenates (P<0.05). Furthermore, the SR Ca(2+)-ATPase expression was inversely correlated to the septum thickness assessed by echocardiography, but not to age, cardiac index or outflow tract gradient. In primary as well as in secondary hypertrophied human myocardium, the expression of SR Ca(2+)-ATPase is reduced and inversely related to the degree of the hypertrophy. The diminished SR Ca(2+)-ATPase expression might result in reduced Ca(2+)reuptake into the SR and might contribute to altered contractile behavior in hypertrophied human myocardium.
authors.affiliation: Department of Cardiology, Medical Faculty, University of Technology, Pauwelsstrasse 30, Aachen, D-52057, Germany. usch@pcserver.mk1.rwth-qqchen.de
authors.forename: U
authors.initials: U
authors.lastname: Schotten
authors.forename: B
authors.initials: B
authors.lastname: Koenigs
authors.forename: M
authors.initials: M
authors.lastname: Rueppel
authors.forename: F
authors.initials: F
authors.lastname: Schoendube
authors.forename: P
authors.initials: P
authors.lastname: Boknik
authors.forename: W
authors.initials: W
authors.lastname: Schmitz
authors.forename: P
authors.initials: P
authors.lastname: Hanrath
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis*; D006332:Cardiomegaly / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D017136:Ion Transport; D008297:Male; D008875:Middle Aged; D012433:Ryanodine / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000473:pathology
chemical_list: D015220:Calcium Channels; D012433:Ryanodine; D000252:Calcium-Transporting ATPases; D002118:Calcium