Document Detail


Inhibition of prolyl 4-hydroxylase prevents left ventricular remodelling in rats with thoracic aortic banding.
MedLine Citation:
PMID:  17145199     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Pressure overload leads to myocardial remodelling with collagen accumulation, left ventricular hypertrophy (LVH), neurohormonal activation and myocardial dysfunction. Prolyl 4-hydroxylases (P4H) are involved in collagen maturation. Inhibition of P4H has been shown to prevent LV remodelling and improve survival post-myocardial infarction.
AIM: To evaluate the role of P4H in pressure overload-induced myocardial remodelling.
METHODS: Male Wistar rats underwent thoracic aortic banding (AoB) and were treated with a P4H inhibitor (P4HI) or vehicle (control). Echocardiography and haemodynamic measurements were performed after 4 weeks. Collagens, matrix metalloproteinases (MMP), tissue inhibitors of MMPs (TIMP), growth factors and neurohormonal markers were quantitated in LV samples.
RESULTS: AoB led to LVH, increased LV enddiastolic pressure (LVEDP) and decreased contractility compared to sham. P4HI reversed these effects. AoB increased collagen I and III expression, which was normalized by P4HI. AoB led to deregulation of matrix remodelling enzymes, enhanced expression of growth factors and activation of the endothelin system. P4HI partially prevented deregulation of the MMP/TIMP system, inhibited upregulation of growth factors and normalized AoB-induced ECE-1 and ETB expression.
CONCLUSIONS: P4HI leads to an improvement of AoB-associated LV dysfunction and reduces imbalance of extracellular matrix turnover and hypertrophy-associated gene expression. P4H inhibition could therefore be of value in treatment of myocardial remodelling accompanying pressure overload hypertrophy.
Authors:
Jens Fielitz; Sebastian Philipp; Lars Roman Herda; Evelyn Schuch; Bernhard Pilz; Carola Schubert; Volkmar Günzler; Roland Willenbrock; Vera Regitz-Zagrosek
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-12-04
Journal Detail:
Title:  European journal of heart failure     Volume:  9     ISSN:  1388-9842     ISO Abbreviation:  Eur. J. Heart Fail.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-26     Completed Date:  2007-11-13     Revised Date:  2011-06-08    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  336-42     Citation Subset:  IM    
Affiliation:
Department of Cardiology, CVK, Charite, Universitätsmedizin Berlin, and St. Elisabeth Hospital, Halle, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Thoracic / physiopathology*
Collagen Type I
Collagen Type III
Fibrosis / physiopathology
Heart Ventricles / drug effects,  physiopathology*,  ultrasonography
Hypertrophy, Left Ventricular / physiopathology,  prevention & control*
Male
Matrix Metalloproteinases, Membrane-Associated*
Myocardium
Procollagen-Proline Dioxygenase / antagonists & inhibitors,  drug effects,  therapeutic use*
Rats
Rats, Wistar
Risk Factors
Chemical
Reg. No./Substance:
0/Collagen Type I; 0/Collagen Type III; EC 1.14.11.2/Procollagen-Proline Dioxygenase; EC 3.4.24.-/Matrix Metalloproteinases, Membrane-Associated

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