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Sarcoplasmic Reticulum Genes Are Upregulated in Mild Cardiac Hypertrophy But Downregulated in Severe Cardiac Hypertrophy Induced by Pressure Overload

https://doi.org/10.1006/jmcc.1996.0149Get rights and content

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 Ca2+-ATPase, ryanodine receptor, calsequestrin andα-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. Ca2+-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 Ca2+-ATPase mRNA level (r=0.67,P<0.001). In contrast, the level of calsequestrin mRNA expression was unaltered and that ofα-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.

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Please address all correspondence to: Masashi Arai, Second Department of Internal Medicine, Gunma University School of Medicine, Showa-machi, Maebashi, Gunma 371, Japan.

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