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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/H2952    most recent 00004.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Xu, X. Articles by Cao, J.-M. Search for Related Content PubMed PubMed Citation Articles by Xu, X. Articles by Cao, J.-M.

Hexarelin suppresses cardiac fibroblast proliferation and collagen synthesis in rat

¹Department of Physiology and Pathophysiology and ²Department of Pathology, Institute of Basic Medical Science, Chinese Academy of Medical Sciences, School of Basic Medical Sciences, Peking Union Medical College, Beijing, China; ³Department of Regional Anatomy, College of Basic Medicine, Jiamusi University, Jiamusi, China; and ⁴Endocrine Cell Biology, Prince Henry's Institute of Medical Research, Melbourne, Australia

Submitted 2 January 2007 ; accepted in final form 24 August 2007

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, ³H-thymidine incorporation, and ³H-proline incorporation. The level of mRNA of transforming growth factor (TGF)- was evaluated by RT-PCR, and the active TGF-1 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 A₂R antagonist) and 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; a specific A₁R 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--induced increase of DNA synthesis in cardiac fibroblast and 2) reduced ANG II-induced upregulation of TGF- mRNA expression and active TGF-1 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 A₂R and diminishment of ANG II-induced increase in TGF- expression and release.

growth hormone secretagogues; growth hormone-releasing peptides; heart