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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.

Abstract：

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.

journal_name

Circulation

journal_title

Circulation

authors

Heymans S,Schroen B,Vermeersch P,Milting H,Gao F,Kassner A,Gillijns H,Herijgers P,Flameng W,Carmeliet P,Van de Werf F,Pinto YM,Janssens S

doi

10.1161/CIRCULATIONAHA.104.516963

subject

Has Abstract

pub_date

2005-08-23 00:00:00

pages

1136-44

issue

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.104.516963

journal_volume

112

pub_type

杂志文章

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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.