Dissociation of left ventricular hypertrophy, beta-myosin heavy chain gene expression, and myosin isoform switch in rats after ascending aortic stenosis

Circulation. 1997 Mar 4;95(5):1253-9. doi: 10.1161/01.cir.95.5.1253.

Abstract

Background: Reexpression of the fetal beta-myosin heavy chain (beta-MHC) gene was reported to be a marker for phenotypic reprogramming and cardiac hypertrophy in rats. Recent in vitro studies strongly suggested a role of angiotensin II for phenotypic reprogramming. In the present investigation, beta-MHC gene expression was studied in an experimental model of pressure-over-load hypertrophy that is not associated with a concurrent activation of the circulating renin-angiotensin system.

Methods and results: Hypertrophy was induced in rats by ascending aortic banding (n = 40). After 7 days, myosin contained 31% (P < .05) of the beta-MHC isoform in banded but < 5% in sham-operated animals. However, no specific elevation of beta-MHC mRNA levels was found in banded animals. In contrast, hearts of rats with abdominal aortic banding displayed a marked increase in beta-MHC mRNA levels (3-fold to 5-fold, P < .05). Both the left ventricular weight and left ventricular peak systolic pressure were significantly elevated compared with sham-operated animals (abdominal aortic banding, +13% and 164 +/- 7 mm Hg; ascending aortic banding, +27% and 191 +/- 9 mm Hg). Plasma renin activity was elevated in rats with abdominal aortic banding (2.5-fold, P < .05) but not in rats with ascending aortic banding.

Conclusions: The results of the present work do not support the concept that increased beta-MHC gene expression is a general "stable late marker" of myocardial hypertrophy in rats. Our results suggest that the stimulation of the renin-angiotensin system is crucial for the activation of the beta-MHC gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Aorta, Abdominal
  • Aorta, Thoracic*
  • Aortic Valve Stenosis / metabolism*
  • Aortic Valve Stenosis / physiopathology
  • Cardiomegaly / metabolism
  • Cardiomegaly / physiopathology
  • Female
  • Heart Ventricles
  • Hemodynamics
  • Hypertrophy, Left Ventricular / metabolism*
  • Hypertrophy, Left Ventricular / physiopathology
  • Myocardium / metabolism*
  • Myosin Heavy Chains / biosynthesis*
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic*

Substances

  • RNA, Messenger
  • Myosin Heavy Chains