Sarcoplasmic reticulum genes are upregulated in mild cardiac hypertrophy but downregulated in severe cardiac hypertrophy induced by pressure overload

J Mol Cell Cardiol. 1996 Aug;28(8):1583-90. doi: 10.1006/jmcc.1996.0149.


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.

Publication types

  • Comparative Study

MeSH terms

  • Actins / genetics
  • Animals
  • Calcium / metabolism
  • Calcium Channels / genetics
  • Calcium-Transporting ATPases / genetics
  • Calmodulin-Binding Proteins / metabolism
  • Calsequestrin / genetics
  • Cardiomegaly / metabolism*
  • Down-Regulation
  • Hemodynamics / physiology
  • Hypertension / physiopathology*
  • Male
  • Muscle Proteins / genetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Ryanodine Receptor Calcium Release Channel
  • Sarcoplasmic Reticulum / genetics*
  • Up-Regulation


  • Actins
  • Calcium Channels
  • Calmodulin-Binding Proteins
  • Calsequestrin
  • Muscle Proteins
  • RNA, Messenger
  • Ryanodine Receptor Calcium Release Channel
  • Calcium-Transporting ATPases
  • Calcium