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(Hypertension. 2001;38:261.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Nitric Oxide Attenuates the Expression of Transforming Growth Factor-ß₃ mRNA in Rat Cardiac Fibroblasts via Destabilization

Nadia Abdelaziz; Federico Colombo; Isabelle Mercier; Angelino Calderone

From the Université de Montréal, Departemént de Physiologie, et l’Institut de Cardiologie de Montréal, Montréal, Québec, Canada.

Correspondence to Angelino Calderone, l’Institut de Cardiologie de Montréal, 5000 rue Belanger est, Montréal, Québec, Canada H1T 1C8. E-mail calderon{at}icm.umontreal.ca

Abstract— Transforming growth factor-ß (TGF-ß) has been implicated in the development of interstitial fibrosis in cardiac hypertrophy. NO has been regarded as a potent inhibitor of cardiac fibroblast growth, albeit the modulation of cellular events associated with interstitial fibrosis remains undefined. In this regard, the regulation of TGF-ß mRNA expression by the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) was examined in neonatal rat cardiac fibroblasts. SNAP treatment for 4 hours decreased TGF-ß₃ mRNA levels, an effect mimicked by 8-bromo-cGMP. TGF-ß₃ mRNA, however, had returned to levels observed in the untreated cells after a 24-hour exposure to SNAP, whereas a decreased expression persisted with 8-bromo-cGMP. In contrast to TGF-ß₃, TGF-ß₁ mRNA levels were modestly increased in response to cGMP-generating molecules. The treatment with actinomycin D for at least 8 hours did not appreciably alter TGF-ß₃ mRNA levels. By contrast, SNAP treatment caused a rapid decrease of TGF-ß₃ mRNA with a half-life of 3.3±0.2 hours, thereby supporting a mechanism of destabilization. The pretreatment with SNAP inhibited angiotensin II-stimulated protein synthesis and the concomitant expression of TGF-ß₃ mRNA. These data reveal a disparate pattern of TGF-ß₁ and TGF-ß₃ mRNA regulation by NO and highlight a novel mechanism of destabilization contributing to the decreased expression of TGF-ß₃ mRNA. The modulation of both basal and angiotensin II-stimulated TGF-ß₃ mRNA expression provides a mechanism by which NO may influence the progression of interstitial fibrosis.

Key Words: nitric oxide • cyclic GMP • fibroblasts • RNA, messenger • transforming growth factors • angiotensin II

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