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Eur J Pharmacol. 2007 Jul 19;567(3):186-92. Epub 2007 Apr 5.

17beta-estradiol inhibits angiotensin II-induced collagen synthesis of cultured rat cardiac fibroblasts via modulating angiotensin II receptors.

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Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.


Circulating endogenous estrogen is considered to be cardiovascular protective, but the underlying mechanisms remain obscure. The cardiac fibroblasts, the most abundant cell type present in the heart, are responsible for the deposition of extracellular matrix. Angiotensin II has been known to stimulate cardiac collagen gene expression. The present study was designed to investigate the effect of 17beta-estradiol on the angiotensin II-induced proliferation and collagen synthesis in cultured cardiac fibroblasts by using real-time polymerase chain reaction (PCR), Western blot and 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide proliferation assay. Angiotensin II increased the cell proliferation and synthesis of collagen types I and III. Angiotensin II up-regulated the gene expression of the angiotensin AT(1) receptor and down-regulated the gene expression of the angiotensin AT(2) receptor in cardiac fibroblasts. The effects of angiotensin II was abolished by the angiotensin AT(1) receptor antagonist, losartan, but not by the angiotensin AT(2) receptor antagonist, PD 123319. 17beta-estradiol prevented increases in proliferation and attenuated the collagen synthesis in response to angiotensin II. The increased AT(1) receptor mRNA levels and decreased AT(2) receptor mRNA levels were partially reversed by 17beta-estradiol treatment. In conclusion, the down-regulation of angiotensin AT(1) receptor expression and function is likely to be an important mechanism accounting for the inhibitory effect of 17beta-estradiol on angiotensin II-stimulated proliferation and collagen synthesis in cardiac fibroblasts. This effect may confer at least in part the cardiac protective action of 17beta-estradiol under pathological conditions with increased activity of the rennin-angiotensin system.

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