title: Sarcoplasmic reticulum genes are upregulated in mild cardiac hypertrophy but downregulated in severe cardiac hypertrophy induced by pressure overload.
abstract: Changes in contractile and relaxation properties of heart muscle in the cardiac hypertrophy induced by pressure overload have been attributed to alterations in intracellular Ca2+ transport as well as the phenotypic and quantitative changes in contractile protein. However, contradictory data have been reported regarding Ca2+ uptake, release and storage by the sarcoplasmic reticulum (SR). The purpose of this study was to evaluate the changes in SR Ca(2+)-ATPase, ryanodine receptor, calsequestrin and alpha-actin gene expression, and the changes in Ca2+ uptake capacity in various degrees of hypertrophied hearts due to pressure overload. Cardiac hypertrophy was produced in rats by placing a constricting clip (0.80 mm) around the suprarenal abdominal aorta for 8 days. The mRNA levels and Ca2+ uptake capacity were then measured as a function of the severity of cardiac hypertrophy. Ca(2+)-ATPase and ryanodine receptor mRNA levels were increased in mildly hypertrophied hearts but were diminished in severely hypertrophied hearts, showing a bimodal response to pressure overload, Ca2+ uptake capacity showed similar changes along with a positive correlation with Ca(2+)-ATPase mRNA level (r = 0.67, P < 0.001). In contrast, the level of calsequestrin mRNA expression was unaltered and that of alpha-actin was markedly increased over a range of severity of cardiac hypertrophy. These findings suggest that the expression of sarcoplasmic reticulum genes for Ca2+ uptake and release is up- or downregulated dependent on the degree of pressure overload. The gene for the SR Ca2+ storage protein, calsequestrin, might be under different control from these genes in pressure overload. Our findings suggest that the decrease in ratio of mRNAs encoding Ca2+ uptake and release proteins to those encoding contractile proteins could significantly contribute to the slowed contractile and relaxation properties seen in pressure-overloaded hearts.
authors.affiliation: Second Department of Internal Medicine, Gunma University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Arai
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: R
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics; D000252:Calcium-Transporting ATPases / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002155:Calsequestrin / Q000235:genetics; D006332:Cardiomegaly / Q000378:metabolism*; D015536:Down-Regulation; D006439:Hemodynamics / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D000199:Actins; D015220:Calcium Channels; D002148:Calmodulin-Binding Proteins; D002155:Calsequestrin; D009124:Muscle Proteins; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D000252:Calcium-Transporting ATPases; D002118:Calcium