Cardiac hypertrophy-induced changes in mRNA levels for TGF-beta 1, fibronectin, and collagen.
Cardiac hypertrophy induced by pressure overload is accompanied by increases in the deposition of extracellular matrix (ECM) proteins. We wanted to determine in this study whether changes in mRNA coding for transforming growth factor (TGF)-beta 1, TGF-beta 3, and the ECM proteins, fibronectin and collagen, occur during the early phases of cardiac hypertrophy. Steady-state mRNA levels were determined in sham-operated and thoracic-banded hypertrophied rat myocardium from 6 h to 30 days after surgery. TGF-beta 1 mRNA increased significantly (1.7-fold vs. control) 12 h after aortic banding, decreasing to control levels by 14 days. No significant changes were observed for TGF-beta 3 message. Fibronectin mRNA levels increased twofold at day 1 and peaked to approximately threefold at day 3. Type I and III collagen mRNA expression was similar to control levels at day 1 but increased significantly 3 days after banding. Cardiac hypertrophy also resulted in an induction of mRNA for an embryonic isoform of fibronectin (EIIIA+) that is generated through alternative splicing of the gene. These findings indicate that, with myocardial hypertrophy, mRNAs for fibronectin are increased as early as 1 day after banding, which may allow for an initial increase in the production of fibronectin followed by the deposition of collagen. These increased mRNA levels for the ECM proteins are preceded by marked increases in TGF-beta 1 mRNAs.
Villarreal
F J
FJ
Department of Medicine, University of California, San Diego 92103.
Dillmann
W H
WH
D000818:Animals; D015152:Blotting, Northern; D006332:Cardiomegaly / Q000235:genetics*; D003094:Collagen / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics*; D006706:Homeostasis; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016212:Transforming Growth Factor beta / Q000235:genetics*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen