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PMID: 7929822 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Hypertrophic stimuli induce transforming growth factor-beta 1 expression in rat ventricular myocytes.

The Journal of clinical investigation ·Vol. 94 ·No. 4 ·1994-10-00 ·Pages 1470-6

Takahashi N, Calderone A, Izzo NJ, Mäki TM, Marsh JD, Colucci WS

Abstract

Transforming growth factor-beta 1 (TGF-beta 1) is a peptide growth factor that may play a role in the myocardial response to hypertrophic stimuli. However, the cellular distribution, mechanism of induction, and source of increased TGF-beta 1 in response to hypertrophic stimuli are not known. We tested the hypothesis that the cardiac myocyte responds to hypertrophic stimuli with the increased expression of TGF-beta 1. In adult rat ventricular myocardium freshly dissociated into myocyte and nonmyocyte cellular fractions, the preponderance of TGF-beta 1 mRNA visualized by Northern hybridization was in the nonmyocyte fraction. Abdominal aortic constriction (7 d) and subcutaneous norepinephrine infusion (36 h) each caused ventricular hypertrophy associated with 3.1-fold and 3.8-fold increases, respectively, in TGF-beta 1 mRNA in the myocyte fraction, but had no effect on the level of TGF-beta 1 mRNA in the nonmyocyte fraction. In ventricular myocytes, norepinephrine likewise caused a 4.1-fold increase in TGF-beta 1 mRNA associated with an increase in TGF-beta bioactivity. This induction of TGF-beta 1 mRNA occurred at norepinephrine concentrations as low as 1 nM and was blocked by prazosin, but not propranolol. NE did not increase the TGF-beta 1 mRNA level in nonmyocytes, primarily fibroblasts, cultured from neonatal rat ventricle. Thus, the cardiac myocyte responds to two hypertrophic stimuli, pressure overload and norepinephrine, with the induction of TGF-beta 1. These data support the view that TGF-beta 1, released by myocytes and acting in an autocrine and/or paracrine manner, is involved in myocardial remodeling by hypertrophic stimuli.

MeSH Terms
Animals Animals, Newborn Aorta, Abdominal Atrial Natriuretic Factor/biosynthesis,genetics Cardiomegaly/etiology,metabolism Cells, Cultured Constriction, Pathologic Culture Media, Conditioned/pharmacology Fibroblasts/metabolism Heart Ventricles Male Myocardium/cytology,metabolism Norepinephrine/pharmacology Prazosin/pharmacology Propranolol/pharmacology RNA, Messenger/biosynthesis Rats Rats, Sprague-Dawley Transforming Growth Factor beta/biosynthesis,genetics Up-Regulation/drug effects
Chemicals
Culture Media, Conditioned RNA, Messenger Transforming Growth Factor beta Atrial Natriuretic Factor Propranolol Norepinephrine Prazosin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Takahashi N
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Calderone A
Izzo N J
Mäki T M
Marsh J D
Colucci W S
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI117485
Published
1994-10-00
Pages
1470-6
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295284
Subset
IM
Grants
FIC NIH HHS · F05 TW04685 · United States
NHLBI NIH HHS · HL-35781 · United States
NHLBI NIH HHS · HL-42539 · United States
External Links
PubMed source DOI: 10.1172/JCI117485 PMC Full Text View journal details
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