Abstract:
BACKGROUND AND PURPOSE:The aim of this study was to determine whether the apelin/APJ system is altered in human cardiovascular disease by investigating whether the expression of apelin or its receptor is altered at the protein level. EXPERIMENTAL APPROACH:Radioligand binding studies were used to determine apelin receptor density in human cardiac tissues. Apelin peptide levels in cardiovascular tissues were determined by radioimmunoassay. In vitro pharmacology was used to assess vasoactive properties of apelin in human coronary artery. Localization of apelin and its receptor in coronary artery was determined using immunohistochemistry. KEY RESULTS:Apelin receptor density was significantly decreased in left ventricle from patients with dilated cardiomyopathy or ischaemic heart disease compared with controls, but apelin peptide levels remained unchanged. Apelin was up-regulated in human atherosclerotic coronary artery and this additional peptide localized to the plaque, colocalizing with markers for macrophages and smooth muscle cells. Apelin potently constricted human coronary artery. CONCLUSIONS AND IMPLICATIONS:We have detected changes in the apelin/APJ system in human diseased cardiac and vascular tissue. The decrease in receptor density in heart failure may limit the positive inotropic actions of apelin, contributing to contractile dysfunction. The contribution of the increased apelin levels in atherosclerotic coronary artery to disease progression remains to be determined. These data suggest a potential role for the apelin/APJ system in human cardiovascular disease.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Pitkin SL,Maguire JJ,Kuc RE,Davenport APdoi
10.1111/j.1476-5381.2010.00821.xsubject
Has Abstractpub_date
2010-08-01 00:00:00pages
1785-95issue
7eissn
0007-1188issn
1476-5381pii
BPH821journal_volume
160pub_type
杂志文章abstract::If one drug, B, antagonizes another, A, by producing the opposite physiological effect, the antagonist concentration-effect curves should be affected by the recording system, which limits the range of agonist responses. With pieces of isolated guinea-pig ileum taken from adjacent parts of the same animal, one recorded...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704169
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journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1476-5381.1968.tb07956.x
更新日期:1968-09-01 00:00:00
abstract::1. Comparison of the rank order of potency of the natural prostanoids prostaglandin E2 (PGE2), PGD2, PGF2 alpha and carbaprostacyclin in stimulating cyclic AMP in Jurkat cells is consistent with the presence of an EP receptor. 2. Lack of responsiveness to the EP1/EP3 selective agonist, sulprostone, and the EP2 agonist...
journal_title:British journal of pharmacology
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