| Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia. | |
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MedLine Citation:
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PMID: 17143192 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES:Beta-blockers are widely used and effective for treating hypertension, acute myocardial infarction (MI) and heart failure, but they present side-effects mainly due to antagonism of beta2-adrenergic receptor (AR). Currently available beta-blockers are at best selective but not specific for beta1 or beta2-AR. METHODS: To specifically inhibit the expression of the beta1-AR, we developed a small interfering RNA (siRNA) targeted to beta1-AR. Three different sequences of beta1 siRNA were delivered into C6-2B cells with 90% efficiency. RESULTS: One of the three sequences reduced the level of beta1-AR mRNA by 70%. The siRNA was highly specific for beta1-AR inhibition with no overlap with beta2-AR. To test this in vivo, systemic injection of beta1 siRNA complexed with liposomes resulted in efficient delivery into the heart, lung, kidney and liver, and effectively reduced beta1-AR expression in the heart without altering beta2-AR. beta1 siRNA significantly lowered blood pressure of spontaneously hypertensive rats (SHR) for at least 12 days and reduced cardiac hypertrophy following a single injection. Pretreatment with beta1 siRNA 3 days before induction of MI in Wistar rats significantly improved cardiac function, as demonstrated by dP/dt and electrocardiogram following the MI. The protective mechanism involved reduction of cardiomyocyte apoptosis in the beta1 siRNA-treated hearts. CONCLUSIONS: The present study demonstrates the possibility of using siRNA for treating cardiovascular diseases and may represent a novel beta-blocker specific for beta1-AR. |
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Authors:
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Anne-Sophie Arnold; Yao Liang Tang; Keping Qian; Leping Shen; Valery Valencia; Michael Ian Phillips; Yuan Clare Zhang |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of hypertension Volume: 25 ISSN: 0263-6352 ISO Abbreviation: J. Hypertens. Publication Date: 2007 Jan |
Date Detail:
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Created Date: 2006-12-04 Completed Date: 2007-03-02 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 197-205 Citation Subset: IM |
Affiliation:
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Children's Research Institute, Department of Pediatrics, University of South Florida, Saint Petersburg, FL 33701, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antihypertensive Agents / metabolism*, therapeutic use Apoptosis Blood Pressure* Cell Line, Tumor Disease Models, Animal Heart Ventricles / pathology Hypertension / genetics, metabolism*, pathology, physiopathology Male Mice Myocardial Ischemia / genetics, metabolism*, pathology, physiopathology Myocardium / metabolism RNA Interference* RNA, Messenger / metabolism RNA, Small Interfering / genetics, metabolism*, therapeutic use Rats Rats, Inbred SHR Rats, Wistar Receptors, Adrenergic, beta-1 / genetics, metabolism* Time Factors Transfection Ventricular Function, Left |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL67248/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Receptors, Adrenergic, beta-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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