Cellular mechanisms of left ventricular hypertrophy

J Mel

Cell Cardiol 24 (Supplement II) (1992)

II-1

Intracellular

signaling

of cardiac

cellular

hypertrophy

due

to

mechanical

stimuli. Yoshio Third

Yazaki. Department

Issei Komuro. of Internal

Eitetsu Medicine,

Hoh and Ryozo h’agai University of Tokyo,

Tokyo,

Japan

To examine the molecular mechanisms by which mechanical stimuli induce we cultured rat neonatal cardiocytes in deformable protooncogene expression, dishes and imposed an in vitro mechanical load by stretching the adherent cells. Hyocyte stretching increased total cell RNA content and nRNA levels of c-fos and skeletal a-actin followed by activation of protein synthesis. CAT assay indicated that sequences containing a serum response element were required for efficient transcription of c-fos gene by stretching. This accumulation of c-fos q RIiA was suppressed by protein kinase C inhibitors at the transcriptional level and inhlblted markedly by down-regulation of protein kinase C. Moreover. wocyte stretching increased inositol phosphate levels. These findings suggest that mechanical stimuli might directly induce protooncogene expression possibly via protein kinase C activation. Furthermore, we observed the activation of MAP kinase by myocytes stretching. This result suggest that MAP kinase activation might increase in efficiency of protein synthesis on ribosomes induced by mechanical stlmull.

II-2

Cellular

mechanisms

of left ventricular

hypertrophy.

Bernard Swynghedauw. U 127 - INSERM - H6pital Lariboisibre - 41 BD de la Chapelle - 75010 Paxis, France. The hypertensive cardiopathy is one example, amongst several, of the general process of biological adaptation. Any adaptation to environmental requirements proceeds by trials and errors and involves changes in gene expression which can be benefitial, detrimental or even useless. Cardiac hypertrophy results from a cascade of events which includes : a trigger, a transmitter, a txansient change in gene expression and a permanent change in the expression of the genes coding for membrane, contracile or mitochondrial proteins. Most of these modifications are due to the re-expression of the foe.tal pmgrame. Cardiac adaptation is a consequence of both hypertrophy and the slowing of Vmax. The slowing of Vmax is a consequence of a change in the phenotype of isomyosins and/or membrane proteins depending of the species. The modifications of the membrane phenotype are complex and the resulting hypertrophied myocyte is in an unstable situation in terms of calcium homeostasis. This new situation may favor arrhythmias.

II-3

THE

EXPRESSION OF Kawaguchi,

ANCIOTENSINOGEN

IN

CARDIOMYOPATHIC

HAMSTER

Kudo. Hi toshi San0, Hiroshi Mikako Shoki, Akira Kitabatake. Yasuda, of Cardiovascular Medicine, Hokkaido University cardiomyopathic hamsters (BIO 14. 6 and BIO 53. 58) hereditary abnormalities of the cardiac and skeletal muscles. In this report, we determined the role of angiotensin in cardiomyopathic hamster hearts. The expression of angiotensinogen mRNA was observed in hamster heart. There was no differences in its expression level between Flb. BIO14. 6 and BIO 53. 58. There was no effect of ages on its expression in these hamster hearts. We have also determined the distribution of angiotensinogen in these hamsters. At 4 weeks old of age, revealed that the immunohistochemical study angiotensinogen widely distributed in subendcardium in these hamsters. There was no difference in its distribution between Flb, B1014. 6 and B1053.58. But at 20 weeks old of age in BIO 53.58 it decreased. There was no effect of age on its reactivity in Flb and BIO 14. 6. We have detected angiotensinogen in heart. but its role is not still clear. The further study should be done to clarify its role on cardiac hypertrophy and cell damage.

Hideaki Okamoto, Department Syrian display

Toshiyuki Hisashi

S.69