Subcellular remodeling and heart dysfunction in cardiac hypertrophy due to pressure overload.
Rats were treated with etomoxir, an inhibitor of palmitoyltransferase-1, to examine the role of a shift in myocardial metabolism in cardiac hypertrophy. Pressure overload was induced by abdominal aorta banding for 8 weeks. Sham-operated animals served as control. Left ventricular dysfunction, as reflected by decreased LVDP, +dP/dt, -dP/dt, and elevated LVEDP in the pressure overloaded animals, was improved by treatment with etomoxir. Cardiac hypertrophy in pressure-overload rats decreased the sarcoplasmic reticular (SR) Ca2+ uptake and Ca2+ release as well as myofibrillar Ca(2+)-stimulated ATPase and myosin Ca(2+)-ATPase activities; these changes were attenuated by treatment with etomoxir. Steady-state mRNA levels for alpha- and beta-myosin heavy chains, SR Ca(2+)-pump, and protein content of SR Ca(2+)-pump were reduced in hypertrophied hearts; these alterations were prevented by etomoxir treatment. The results indicate that modification of changes in myocardial metabolism by etomoxir may prevent remodeling of myofibrils and SR membrane and thereby improve cardiac function in hypertrophied heart.
Dhalla
N S
NS
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnepeg, Manitoba, Canada.
Golfman
L
L
Liu
X
X
Sasaki
H
H
Elimban
V
V
Rupp
H
H
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics; D006332:Cardiomegaly / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D015870:Gene Expression / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D006973:Hypertension / Q000150:complications*; D009206:Myocardium / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D020257:Ventricular Remodeling / Q000502:physiology*
D020033:Protein Isoforms; D018995:Myosin Heavy Chains; D000252:Calcium-Transporting ATPases