| Metoprolol treatment lowers thrombospondin-4 expression in rats with myocardial infarction and left ventricular hypertrophy. | |
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MedLine Citation:
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PMID: 20353484 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thrombospondins are matrix proteins linked to extracellular matrix remodelling but their precise role in the heart is not known. In this study, we characterised left ventricular thrombospondin-1 and -4 expression in rats treated with a beta-blocker metoprolol during the remodelling process in response to pressure overload and acute myocardial infarction. Left ventricular thrombospondin-1 and thrombospondin-4 mRNA levels increased 8.4-fold (p < 0.001) and 7.3-fold (p < 0.001) post-infarction, respectively. Metoprolol infusion by osmotic minipumps (1.5 mg/kg/hr) for 2 weeks after myocardial infarction decreased thrombospondin-1 and thrombospondin-4 mRNA levels (55% and 50%, respectively), improved left ventricular function, and attenuated left ventricular remodelling with reduction of left ventricular atrial natriuretic peptide and brain natriuretic peptide gene expression. Thrombospondin-1 and -4 mRNA levels correlated positively with echocardiographic parameters of left ventricular remodelling as well as with atrial natriuretic peptide and brain natriuretic peptide gene expression. Moreover, there was a negative correlation between left ventricular ejection fraction and thrombospondin-1 mRNA levels. In 12-month-old spontaneously hypertensive rats with left ventricular hypertrophy, metoprolol decreased left ventricular thrombospondin-4 levels and attenuated remodelling while thrombospondin-1, atrial natriuretic peptide and brain natriuretic peptide mRNA levels as well as left ventricular function remained unchanged. In metoprolol-treated spontaneously hypertensive rats, thrombospondin-4 gene expression correlated with parameters of left ventricular remodelling, while no correlations between thrombospondins and natriuretic peptides were observed. These results indicate that thrombospondin-1 expression is linked exclusively to left ventricular remodelling process post-infarction while thrombospondin-4 associates with myocardial remodelling both after myocardial infarction and in hypertensive heart disease suggesting that thrombospondins may have unique roles in extracellular matrix remodelling process. |
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Authors:
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Erja Mustonen; Hanna Leskinen; Jani Aro; Marja Luodonpää; Olli Vuolteenaho; Heikki Ruskoaho; Jaana Rysä |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-28 |
Journal Detail:
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Title: Basic & clinical pharmacology & toxicology Volume: 107 ISSN: 1742-7843 ISO Abbreviation: Basic Clin. Pharmacol. Toxicol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-17 Completed Date: 2010-12-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101208422 Medline TA: Basic Clin Pharmacol Toxicol Country: Denmark |
Other Details:
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Languages: eng Pagination: 709-17 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Institute of Biomedicine, Biocenter Oulu, University of Oulu, Oulu, Finland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antihypertensive Agents / therapeutic use* Hypertension / drug therapy, metabolism Hypertrophy, Left Ventricular / drug therapy*, metabolism, ultrasonography Male Metoprolol / therapeutic use* Myocardial Infarction / drug therapy*, metabolism RNA, Messenger / metabolism Rats Rats, Inbred SHR Rats, Sprague-Dawley Thrombospondins / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/RNA, Messenger; 0/Thrombospondins; 0/thrombospondin 4; 37350-58-6/Metoprolol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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