Chronic administration of hexarelin attenuates cardiac fibrosis in the spontaneously hypertensive rat

Xu, Xiangbin, Ding, Fan, Pang, Jinjiang, Gao, Xue, Xu, Rong-Kun, Hao, Wei, Cao, Ji-Min and Chen, Chen (2012) Chronic administration of hexarelin attenuates cardiac fibrosis in the spontaneously hypertensive rat. American Journal of Physiology Heart and Circulatory Physiology, 303 6: H703-H711. doi:10.1152/ajpheart.00257.2011

Author Xu, Xiangbin
Ding, Fan
Pang, Jinjiang
Gao, Xue
Xu, Rong-Kun
Hao, Wei
Cao, Ji-Min
Chen, Chen
Title Chronic administration of hexarelin attenuates cardiac fibrosis in the spontaneously hypertensive rat
Journal name American Journal of Physiology Heart and Circulatory Physiology   Check publisher's open access policy
ISSN 0363-6135
Publication date 2012-09-15
Sub-type Article (original research)
DOI 10.1152/ajpheart.00257.2011
Volume 303
Issue 6
Start page H703
End page H711
Total pages 9
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Collection year 2013
Language eng
Abstract 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 (GHSs) possessing a variety of cardiovascular effects via action on GHS receptors (GHS-Rs). However, the role of hexarelin in cardiac fibrosis in vivo has not yet been investigated. In the present study, spontaneously hypertensive rats (SHRs) were treated with hexarelin alone or in combination with a GHS-R antagonist for 5 wk from an age of 16 wk. Hexarelin treatment significantly reduced cardiac fibrosis in SHRs 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 hearts. Hexarelin treatment also increased matrix metalloproteinase (MMP)-2 and MMP-9 activities and decreased myocardial mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1 in SHRs. In addition, hexarelin treatment significantly attenuated left ventricular (LV) hypertrophy, LV diastolic dysfunction, and high blood pressure in SHRs. The effect of hexarelin on cardiac fibrosis, blood pressure, and cardiac function was mediated by its receptor, GHS-R, since a selective GHS-R antagonist abolished these effects and expression of GHS-Rs was upregulated by hexarelin treatment. In summary, our data demonstrate that hexarelin reduces cardiac fibrosis in SHRs, 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 SHRs. The present findings provided novel insights and underscore the therapeutic potential of hexarelin as an antifibrotic agent for the treatment of cardiac fibrosis.
Keyword Cardiac fibrosis
Matrix metalloproteinases
Tissue inhibitors of metalloproteinases
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
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