| Increased cardiac expression of tissue inhibitor of metalloproteinase-1 and tissue inhibitor of metalloproteinase-2 is related to cardiac fibrosis and dysfunction in the chronic pressure-overloaded human heart. | |
| | |
MedLine Citation:
|
PMID: 16103240 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Alterations in the balance of matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) are involved in left ventricular (LV) remodeling. Whether their expression is related to interstitial fibrosis or LV dysfunction in patients with chronic pressure overload-induced LV hypertrophy, however, is unknown. METHODS AND RESULTS: Therefore, cardiac biopsies were taken in 36 patients with isolated aortic stenosis (AS) and in 29 control patients without LV hypertrophy. Microarray analysis revealed significantly increased mRNA expression of collagen types I, III, and IV and transcripts involved in collagen synthesis, including procollagen endopeptidase and lysine and proline hydroxylases, in AS compared with control patients. Collagen deposition was greater in AS than in control patients and was most pronounced in AS patients with severe diastolic dysfunction. Cardiac mRNA expression of TIMP-1 and TIMP-2 was significantly increased in AS compared with control patients (mRNA transcript levels normalized to GAPDH: TIMP-1, 0.67+/-0.1 in AS versus 0.37+/-0.08 in control patients; TIMP-2, 9.5+/-2.6 in AS versus 1.6+/-0.4 in control patients; P<0.05 for both) but did not differ significantly for MMP-1, -2, or -9. Cardiac TIMP-1 and -2 transcripts were significantly related to the degree of interstitial fibrosis and proportional to diastolic dysfunction in AS patients. CONCLUSIONS: Cardiac expression of TIMP-1 and TIMP-2 is significantly increased in chronic pressure-overloaded human hearts compared with controls and is related to the degree of interstitial fibrosis. |
| | |
Authors:
|
Stephane Heymans; Blanche Schroen; Pieter Vermeersch; Hendrik Milting; Fangye Gao; Astrid Kassner; Hilde Gillijns; Paul Herijgers; Willem Flameng; Peter Carmeliet; Frans Van de Werf; Yigal M Pinto; Stefan Janssens |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-08-15 |
Journal Detail:
|
Title: Circulation Volume: 112 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2005 Aug |
Date Detail:
|
Created Date: 2005-08-23 Completed Date: 2006-02-15 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
|
Languages: eng Pagination: 1136-44 Citation Subset: AIM; IM |
Affiliation:
|
CARIM, University Hospital Maastricht, Maastricht, The Netherlands. s.heymans@cardio.unimaas.nl |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aortic Valve Stenosis
/
pathology,
physiopathology Biopsy Chronic Disease Collagen Type I / genetics Collagen Type III / genetics Coronary Artery Bypass Fibrosis Gene Expression Humans Hypertension / pathology, physiopathology* Hypertrophy, Left Ventricular / pathology, physiopathology* Matrix Metalloproteinase 2 / genetics Matrix Metalloproteinase 9 / genetics Myocardium / pathology RNA, Messenger / metabolism Tissue Inhibitor of Metalloproteinase-1 / genetics* Tissue Inhibitor of Metalloproteinase-2 / genetics* Ventricular Pressure* |
| Chemical | |
Reg. No./Substance:
|
0/Collagen Type I; 0/Collagen Type III; 0/RNA, Messenger; 0/Tissue Inhibitor of Metalloproteinase-1; 0/collagen type I, alpha 1 chain; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Percutaneous pulmonary valve implantation in humans: results in 59 consecutive patients.
Next Document: Detection of coronary stenoses at rest with myocardial contrast echocardiography.