Document Detail


Hexarelin suppresses high lipid diet and vitamin D3-induced atherosclerosis in the rat.
MedLine Citation:
PMID:  19931584     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Growth hormone-releasing peptides (GHRP) and ghrelin are synthetic and natural ligands of growth hormone secretagogue receptor (GHSR) respectively and are shown to exert protective actions on cardiac dysfunction. Because ghrelin has been reported to inhibit proinflammatory responses in human endothelium and GHSR has been identified in blood vessels, we hypothesized that GHRP could alleviate the development of atherosclerosis (As). Atherosclearosis was induced by a short period (4 days) of vitamin D(3) and chronic (three months) intragastric feeding of high fat emulsion (containing 0.5% propylthiouracil) in adult SD rats. Some As rats received chronic hexarelin (a variant of GHRP) injection (SC BID, 30 days) and normal rats received placebo as control. Significant atherosclerosis developed in animals fed with the emulsion. Serum total cholesterol and LDL-c increased, and HDL-c and aortic nitric oxide (NO) decreased significantly in As group. Hexarelin suppressed the formation of atherosclerotic plaques and neointima, partially reversed serum HDL-c/LDL-c ratio and increased the levels of serum NO and aortic mRNAs of eNOS, GHSR and CD36 in As rats. Hexarelin also decreased [(3)H]-TdR incorporation in cultured vascular smooth muscle cell (VSMC) and calcium sedimentation in aortic wall. Furthermore, foam cell formation induced by ox-LDL was decreased by hexarelin. In conclusion, hexarelin suppresses high lipid diet and vitamin D3-induced atherosclerosis in rats, possibly through upregulating HDL-c/LDL-c ratio, vascular NO production and downregulating the VSMC proliferation, aortic calcium sedimentation and foam cell formation. These novel anti-atherosclerotic actions of hexarelin suggest that the peptide might have a clinical potential in treating atherosclerosis.
Authors:
Jinjiang Pang; Qihua Xu; Xiangbin Xu; Hongchao Yin; Rongkun Xu; Shu Guo; Wei Hao; Luya Wang; Chen Chen; Ji-Min Cao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-30
Journal Detail:
Title:  Peptides     Volume:  31     ISSN:  1873-5169     ISO Abbreviation:  Peptides     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-12     Completed Date:  2010-07-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008690     Medline TA:  Peptides     Country:  United States    
Other Details:
Languages:  eng     Pagination:  630-8     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 Elsevier Inc. All rights reserved.
Affiliation:
Department of Physiology, School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing 100005, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / metabolism,  pathology
Atherosclerosis / chemically induced*,  drug therapy*,  pathology
Cholecalciferol / pharmacology*
Dietary Fats / adverse effects*
Female
Ghrelin / metabolism
Humans
Lipoproteins / blood
Male
Muscle, Smooth, Vascular / cytology,  drug effects
Nitric Oxide / metabolism
Nitric Oxide Synthase Type III / genetics,  metabolism
Oligopeptides / therapeutic use*
Random Allocation
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Dietary Fats; 0/Ghrelin; 0/Lipoproteins; 0/Oligopeptides; 10102-43-9/Nitric Oxide; 140703-51-1/hexarelin; 67-97-0/Cholecalciferol; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, rat

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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