[Molecular basis for cardiac functions].

Abstract

Cardiac functions are regulated by both contractile proteins and calcium regulatory proteins. Alterations of these are considered involved in impaired contractile and diastolic functions in hypertrophied hearts. In this study, we analyzed molecular changes during the development of cardiac hypertrophy. Cardiac hypertrophy was induced by constricting the pulmonary artery in rabbits or the aorta in rats. In rabbit right ventricular hypertrophy, protein synthesis was increased to 1.8 times the control 2-4 days after pulmonary constriction. This increase in protein synthesis could be classified as an increase in both capacity and efficiency of synthesis. beta-cardiac myosin heavy chain (beta-MHC) isoform was predominantly expressed and alpha-MHC was suppressed in pressure overload hypertrophy. The switch from alpha- to beta-MHC occurred at the mRNA level. Ca(2+)-ATPase of sarcoplasmic reticulum (SR) is important because it regulates intracellular Ca2+ levels during relaxation. In pressure-overload hypertrophy, the SR Ca(2+)-ATPase was markedly decreased in both the enzyme activities and mRNA levels, while in thyrotoxic hearts both were increased. Interstitial cells also undergo phenotypic modulation which was demonstrated by the induction of nonmuscle-type MHC in pressure-overload hypertrophy. The signal transduction system in cardiac hypertrophy was examined by stretching cardiac myocytes grown on deformable membranes. In our analysis, stretching myocytes stimulated protein kinase C, MAP-II kinase and S6 kinase, all of which may lead to the induction of fetal-type cardiac genes and accelerated protein synthesis. These analyses of subcellular adaptation in cardiac hypertrophy provide important insights into understanding molecular mechanisms of cardiac functions.

• Authors: R Nagai, T Yamazaki, I Shiojima, Y Yazaki
• Journal: Rinsho byori. The Japanese journal of clinical pathology (Rinsho Byori) Vol. 41 Issue 4 Pg. 409-14 (Apr 1993) ISSN: 0047-1860 [Print] Japan
• PMID: 8350501 (Publication Type: Journal Article)

Chemical References

• RNA, Messenger
• Myosins
• Calcium-Transporting ATPases

Topics

• Animals
• Calcium-Transporting ATPases (metabolism)
• Heart (physiology, physiopathology)
• Hypertrophy, Left Ventricular (metabolism, physiopathology)
• Hypertrophy, Right Ventricular (metabolism, physiopathology)
• Myocardium (metabolism)
• Myosins (genetics, metabolism)
• RNA, Messenger (metabolism)
• Rabbits
• Rats