Document Detail

Metoprolol treatment lowers thrombospondin-4 expression in rats with myocardial infarction and left ventricular hypertrophy.
MedLine Citation:
PMID:  20353484     Owner:  NLM     Status:  MEDLINE    
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.
Erja Mustonen; Hanna Leskinen; Jani Aro; Marja Luodonpää; Olli Vuolteenaho; Heikki Ruskoaho; Jaana Rysä
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-28
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  107     ISSN:  1742-7843     ISO Abbreviation:  Basic Clin. Pharmacol. Toxicol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-17     Completed Date:  2010-12-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  709-17     Citation Subset:  IM    
Department of Pharmacology and Toxicology, Institute of Biomedicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
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MeSH Terms
Antihypertensive Agents / therapeutic use*
Hypertension / drug therapy,  metabolism
Hypertrophy, Left Ventricular / drug therapy*,  metabolism,  ultrasonography
Metoprolol / therapeutic use*
Myocardial Infarction / drug therapy*,  metabolism
RNA, Messenger / metabolism
Rats, Inbred SHR
Rats, Sprague-Dawley
Thrombospondins / genetics,  metabolism*
Reg. No./Substance:
0/Antihypertensive Agents; 0/RNA, Messenger; 0/Thrombospondins; 0/thrombospondin 4; 37350-58-6/Metoprolol

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