on August 23, 2004
Published online before print August 23, 2004, doi: 10.1161/01.HYP.0000141414.87026.4d
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Submitted on March 4, 2004
From the Carl Ludwig Institute of Physiology (W.B., L.H., B.R., B.Z.-M., H.M., A.D., H.-G.Z.), the Institute of Pathology (A.T.), the Division of Hematology and Oncology (S.L.), and the Department of Dermatology (A.S.), University of Leipzig, Germany. * To whom correspondence should be addressed. E-mail: briestw{at}medizin.uni.
Abstract--Transforming growth factor-
Revised on April 7, 2004
Norepinephrine-Induced Changes in Cardiac Transforming Growth Factor-
Wilfried Briest*; 
Isoform Expression Pattern of Female and Male Rats
ler;
(TGF-) is a ubiquitous growth-regulating protein with an essential role in tissue repair and formation of extracellular matrix (ECM). To better understand the role of different isoforms of TGF- in the cardiac remodeling process induced by norepinephrine (NE), the expression of TGF-1, TGF-2, and TGF-3 was studied and compared with the expression of collagen. NE (0.1 mg/kg · h) was intravenously infused in female and male Sprague-Dawley rats for several time periods, and freshly obtained ventricular myocardium after 1 day was dissociated into myocyte and nonmyocyte fractions. Prazosin (0.1 mg/kg · h) and metoprolol (1 mg/kg · h) were used to block 
- and -adrenoceptors, respectively. After NE infusion, the three isoforms of TGF- were differentially induced as far as the magnitude and the time course is concerned. The increased expression of TGF-2 started earlier with a maximum after 12 hours and was more pronounced (10-fold elevation) than that of the other two isoforms, with a clear specificity for the left ventricle in female hearts. This specificity was also seen in male rats with 16-fold elevation of TGF-2 after 1 day of NE-stimulation. The increase of TGF-2 was significant only in the myocyte fraction obtained from female as well as from male hearts. The expression of the mRNA of all TGF- isoforms of collagen type I and type III, and of the matrix metalloproteinase (MMP)-2 and its inhibitor TIMP-2 was reduced predominantly by -adrenoceptor blockade with prazosin. The increase in TGF- isoforms correlated with that of the mRNA expression of collagens, MMP-2 and TIMP-2.
Key words: adrenergic antagonists • gene expression • extracellular matrix • catecholamine • collagen
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