Hexarelin suppresses cardiac fibroblast proliferation and collagen synthesis in rat.

Hexarelin suppresses cardiac fibroblast proliferation and collagen synthesis in rat. Research Abstract Details 

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Hexarelin suppresses cardiac fibroblast proliferation and collagen synthesis in rat. Abstract Text:

Xiangbin Xu,Jinjiang Pang,Hongchao Yin,Meixiu Li,Wei Hao,Chen Chen,Ji-Min Cao,Xiangbin Xu,Jinjiang Pang,Hongchao Yin,Meixiu Li,Wei Hao,Chen Chen,Ji-Min Cao,

Abnormal growth of cardiac fibroblasts is critically involved in the pathophysiology of cardiac hypertrophy/remodeling. Hexarelin is a synthetic growth hormone secretagogue (GHS), which possesses a variety of cardiovascular protective activities mediated via the GHS receptor (GHSR), including improving cardiac dysfunction and remodeling. The cellular and molecular mechanisms underlying the effect of GHS on cardiac fibrosis are, however, not clear. In this report, cultured cardiac fibroblasts from 8-day-old rats were stimulated with ANG II or FCS to induce proliferation. The fibroblast proliferation and DNA and collagen synthesis were evaluated utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, (3)H-thymidine incorporation, and (3)H-proline incorporation. The level of mRNA of transforming growth factor (TGF)-beta was evaluated by RT-PCR, and the active TGF-beta1 release from cardiac fibroblasts was evaluated by ELISA. The level of cellular cAMP was measured by radioimmunoassay. In addition, the effects of 3,7-dimethyl-l-propargylxanthine (DMPX; a specific adenosine receptor A(2)R antagonist) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; a specific A(1)R antagonist) were tested. It was found that incubation with 10(-7) mol/l hexarelin for 24 h 1) inhibited the ANG II-induced proliferation and collagen synthesis and the 5% FCS- and TGF-beta-induced increase of DNA synthesis in cardiac fibroblast and 2) reduced ANG II-induced upregulation of TGF-beta mRNA expression and active TGF-beta1 release from fibroblasts. Hexarelin increased the cellular level of cAMP in cardiac fibroblasts. DMPX (10(-8) mol/l) but not DPCPX abolished the effect of hexarelin on cardiac fibroblast DNA synthesis. It is concluded that hexarelin inhibits DNA and collagen synthesis and proliferation of cardiac fibroblasts through activation of both GHSR and A(2)R and diminishment of ANG II-induced increase in TGF-beta expression and release.

Hexarelin suppresses cardiac fibroblast proliferation and collagen synthesis in rat. Publishing Authors By Initials

X Xu,J Pang,H Yin,M Li,W Hao,C Chen,JM Cao,X Xu,J Pang,H Yin,M Li,W Hao,C Chen,JM Cao,

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Hexarelin suppresses cardiac fibroblast proliferation and collagen synthesis in rat. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of physiology. Heart and circulat

VOLUME: 293

Page Numbers: H2952-8

Journal Abbreviation: Am. J. Physiol. Heart Circ. Ph

ISSN: 0363-6135

DAY: 31

MONTH: 08

YEAR: 2007

Hexarelin suppresses cardiac fibroblast proliferation and collagen synthesis in rat. Information

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LANGUAGE: eng

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AFFILIATION: Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medical Sciences, Peking Union Medical College, Beijing 100005, People's Republic of China.

Country: United States

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MEDLINETA: Am J Physiol Heart Circ Physio

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