Zeitschrift für Kardiologie

, Volume 89, Issue 1, pp 1–6

Molecular basis of cardiac hypertrophy

  • T. Yamazaki
  • Y. Yazaki

DOI: 10.1007/s003920050001

Cite this article as:
Yamazaki, T. & Yazaki, Y. Z Kardiol (2000) 89: 1. doi:10.1007/s003920050001


Cardiac hypertrophy is an adaptive process to an increased hemodynamic overload. When cardiomyocytes cultured on silicone dishes were stretched, second messengers such as protein kinase C (PKC), Raf-1 kinase, and mitogen-activated protein (MAP) kinases were activated, which were followed by increased protein synthesis. Moreover, pretreatment with an angiotensin II (AngII) type 1 receptor antagonist dimished an increase in protein synthesis, MAP kinase activity, and c-fos gene expression induced by the stretching of cardiomyocytes. These suggest the linkage of the cardiac renin-angiotensin system to the formation of pressure-overload hypertrophy. Indeed, in the stretch-conditioned medium the levels of AngII concentration were increased. Also, mechanical stretch enhanced endothelin (ET)-1 release from the cardiomyocytes and activated the Na+/H+ exchanger independently of these vasoactive peptides. In the second part, we examined AngII-induced signaling pathways both in cardiac myocytes and in cardiac fibroblasts. AngII-evoked signal transduction pathways differed between cell types. In cardiac fibroblasts AngII activated MAP kinases through a pathway including the Gβγ subunit of Gi protein, Src, Shc, Grb2, and Ras, while Gq and PKC activation was necessary in cardiac myocytes. We further explored norepinephrine (NE)-induced signaling pathways in cardiac myocytes. NE activated Raf-1 kinase and MAP kinases and increased amino acid uptake in cardiomyocytes of neonatal rats. β-adrenoceptor (AR) stimulation as well and α1-AR stimulation was involved in NE-induced MAP kinase activation. It is noteworthy that unlike in other cell types not only PKC activation but also protein kinase A (PKA) activation increased the activaties of Raf-1 kinase and MAP kinases in cardiac myocytes and induced cell growth. Finally, we observed that β-AR-induced activation of MAP kinases is dependent on both Gs/cAMP/PKA and Gi/Src/Ras signaling pathways and that phosphorylation of β-AR is critical to the cross talk between these signaling pathways.

Key words Cardiac hypertrophy – renin-angiotensin system – norepinephrine – cardiac myocyte

Copyright information

© Steinkopff Verlag 2000

Authors and Affiliations

  • T. Yamazaki
    • 1
  • Y. Yazaki
    • 2
  1. 1.Department of Cardiovascular Medicine and Department of Pharmacoepidemiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 Japan, E-Mail: yama-tky@umin.ac.jpJP
  2. 2.Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan and International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, JapanJP