HYPERTROPHIC STIMULI INDUCE TRANSFORMING GROWTH FACTOR-BETA(1) EXPRESSION IN RAT VENTRICULAR MYOCYTES

被引:173
作者
TAKAHASHI, N
CALDERONE, A
IZZO, NJ
MAKI, TM
MARSH, JD
COLUCCI, WS
机构
[1] BRIGHAM & WOMENS HOSP,DEPT MED,DIV CARDIOVASC,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,BOSTON,MA 02115
关键词
MYOCARDIUM; GROWTH FACTORS; HYPERTROPHY; NOREPINEPHRINE; ALPHA(1)-ADRENERGIC RECEPTORS;
D O I
10.1172/JCI117485
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:1470 / 1476
页数:7
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