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Chronic administration of hexarelin attenuates cardiac fibrosis in the spontaneously hypertensive rat.
MedLine Citation:
PMID:  22842067     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cardiac fibrosis is a hallmark of heart disease and plays a vital role in cardiac remodeling during heart diseases including hypertensive heart disease. Hexarelin is one of a series of synthetic growth hormone secretagogues (GHS) possessing a variety of cardiovascular effects via action on GHS receptors (GHS-R). However, the role of hexarelin in cardiac fibrosis in vivo has not been investigated yet. In the present study, spontaneously hypertensive rats (SHR) were treated with hexarelin alone or in combination with GHS-R antagonist for 5 weeks from age of 16 weeks. Hexarelin treatment significantly reduced cardiac fibrosis in SHR by decreasing interstitial and perivascular myocardial collagen deposition and myocardial hydroxyproline content, and reducing mRNA and protein expression of collagen I and III in SHR heart. Hexarelin treatment also increased MMP-2 and MMP-9 activities, and decreased the myocardial mRNA expression of TIMP-1 in SHR. In addition, hexarelin treatment significantly attenuated left ventricular (LV) hypertrophy, LV diastolic dysfunction and high blood pressure in SHR. The effect of hexarelin on cardiac fibrosis, blood pressure, and cardiac function was mediated by its receptor, GHS-R, since selective GHS-R antagonist abolished these effects, and expression of GHS-R was up-regulated by hexarelin treatment. In summary, our data demonstrate that hexarelin reduces cardiac fibrosis in SHR, perhaps by decreasing collagen synthesis and accelerating collagen degradation via regulation of MMPs/TIMP. Hexarelin-reduced systolic blood pressure may also contribute to this reduced cardiac fibrosis in SHR. The current findings have provided novel insights and therapeutic potential of hexarelin as an anti-fibrotic agent for the treatment of cardiac fibrosis.
Authors:
Xiangbin Xu; Fan Ding; Jinjiang Pang; Xue Gao; Rong-Kun Xu; Wei Hao; Ji-Min Cao; Chen Chen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-27
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Peking Union Medical College.
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