| Down-regulation of cardioprotective bradykinin type-2 receptors in the left ventricle of patients with end-stage heart failure. | |
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MedLine Citation:
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PMID: 12103265 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: We sought to study the expression of bradykinin type-2 receptors (BK-2Rs) in patients with heart failure (HF). BACKGROUND: Recent work in experimental animals has suggested that bradykinin (BK) exerts cardioprotective effects through specific BK-2Rs. However, nothing is known about the regulation of BK-2R expression in the pathogenesis of human HF. METHODS: Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13) and from normal hearts (n = 6) unsuitable for donation. The patients had HF due to idiopathic dilated cardiomyopathy (IDC) (n = 7) or coronary heart disease (CHD) (n = 6). Tissue samples from the left ventricles were analyzed by competitive reverse-transcriptase-polymerase chain reaction and Western blotting for the expression of BK-2R messenger ribonucleic acid (mRNA) and protein. RESULTS: In both the IDC and CHD hearts, the level of BK-2R mRNA expression was found to be significantly lower (30% and 38% of control values, respectively) than that in normal hearts. Correspondingly, the BK-2R protein level was significantly reduced in both the IDC and CHD hearts (45% and 62% of control values, respectively) and apparently involved all myocardial cell types. The down-regulation of BK-2R expression in failing hearts did not correlate with decreased cellularity or with the expression pattern of other members of the G-protein-coupled receptor superfamily. However, BK-2R down-regulation in the failing hearts was associated with a decrease in endothelial nitric oxide synthase in both IDC (53% of control value) and CHD (43% of control value) hearts. CONCLUSIONS: These results are the first to suggest that a loss of BK-2Rs is involved in the pathogenesis of human HF. |
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Authors:
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Antti Kuoppala; Naotaka Shiota; Jorma O Kokkonen; Inka Liesmaa; Karam Kostner; Mikko Mäyränpää; Petri T Kovanen; Ken A Lindstedt |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of the American College of Cardiology Volume: 40 ISSN: 0735-1097 ISO Abbreviation: J. Am. Coll. Cardiol. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-09 Completed Date: 2002-07-26 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8301365 Medline TA: J Am Coll Cardiol Country: United States |
Other Details:
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Languages: eng Pagination: 119-25 Citation Subset: AIM; IM |
Affiliation:
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Wihuri Research Institute, Helsinki, Finland. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Blotting, Western Cardiomyopathy, Dilated / metabolism Coronary Disease / metabolism Down-Regulation Female Heart Failure / etiology, metabolism* Humans Male Middle Aged Myocardium / metabolism Nitric Oxide Synthase / biosynthesis Nitric Oxide Synthase Type III RNA, Messenger / genetics Receptor, Bradykinin B2 Receptors, Bradykinin / genetics, metabolism*, physiology Reverse Transcriptase Polymerase Chain Reaction Ventricular Function, Left / physiology* |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/Receptor, Bradykinin B2; 0/Receptors, Bradykinin; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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