Regulation of procollagen metabolism in the pressure-overloaded rat heart.
To determine the molecular events responsible for the disproportionate accumulation of myocardial fibrillar collagens during sustained hypertension, we examined the in vivo rate of procollagen synthesis, collagen accumulation, and intracellular procollagen degradation 1-16 wk after abdominal aortic banding in young rats. These measurements were correlated with tissue mRNA levels for type I and type III procollagen polypeptides. Banded animals developed moderate, sustained hypertension and mild left ventricular hypertrophy. Increased type III procollagen mRNA levels were detected early after banding and persisted for the entire observation period. Disproportionate collagen accumulation without histological evidence of fibrosis was noted within 1 wk after hypertension induction. Fibrillar collagen accumulation at this time point resulted not from a major increase in procollagen synthesis, but rather a marked decrease in the rate of intracellular procollagen degradation. Interstitial fibrosis, however, was observed 16 wk after banding. Type I procollagen mRNA levels were increased six-fold, but only after 16 wk of hypertension. These results correlated well with the results of in vivo procollagen synthesis experiments at 16 wk, which demonstrated a threefold increase in left ventricular procollagen biosynthesis. We conclude that pretranslational as well as posttranslational mechanisms regulate fibrillar collagen deposition in the myocardial extracellular matrix during sustained hypertension.
Eleftheriades
E G
EG
Department of Medicine, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Durand
J B
JB
Ferguson
A G
AG
Engelmann
G L
GL
Jones
S B
SB
Samarel
A M
AM
D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology; D001794:Blood Pressure; D001835:Body Weight; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009929:Organ Size; D011347:Procollagen / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors
D011347:Procollagen; D012333:RNA, Messenger