| RRC ID |
24
|
| 著者 |
Matsusaka H, Ikeuchi M, Matsushima S, Ide T, Kubota T, Feldman AM, Takeshita A, Sunagawa K, Tsutsui H.
|
| タイトル |
Selective disruption of MMP-2 gene exacerbates myocardial inflammation and dysfunction in mice with cytokine-induced cardiomyopathy.
|
| ジャーナル |
Am J Physiol Heart Circ Physiol
|
| Abstract |
Tumor necrosis factor-alpha (TNF-alpha) plays a pathophysiological role in the development and progression of heart failure. Matrix metalloproteinase (MMP)-2 is involved in extracellular matrix remodeling. Recent evidence suggests a protective role for this protease against tissue inflammation. Although MMP-2 is upregulated in the failing heart, little is known about its pathophysiological role. We thus hypothesized that ablation of the MMP-2 gene could affect cardiac remodeling and failure in TNF-alpha-induced cardiomyopathy. We crossed transgenic mice with cardiac-specific overexpression of TNF-alpha (TG) with MMP-2 knockout (KO) mice. Four groups of male and female mice were studied: wild-type (WT) with wild MMP-2 (WT/MMP(+/+)), WT with MMP-2 KO (WT/MMP(-/-)), TNF-alpha TG with wild MMP-2 (TG/MMP(+/+)), and TG with MMP-2 KO (TG/MMP(-/-)). The upregulation of MMP-2 zymographic activity in TG/MMP(+/+) mice was completely abolished in TG/MMP(-/-) mice, and other MMPs and tissue inhibitors of metalloproteinase were comparable between groups. Survival was shorter for male TG/MMP(-/-) than TG/MMP(+/+) mice. Female TG/MMP(-/-) mice were more severely affected than TG/MMP(+/+) mice with diminished cardiac function. Myocardial TNF-alpha and other proinflammatory cytokines were increased in TG/MMP(+/+) mice, and this increase was similarly observed in TG/MMP(-/-) mice. The extent of myocardial infiltrating cells including macrophages was greater in TG/MMP(-/-) than in TG/MMP(+/+) mice. Selective ablation of the MMP-2 gene reduces survival and exacerbates cardiac failure in association with the increased level of myocardial inflammation. MMP-2 may play a cardioprotective role in the pathogenesis of cytokine-induced cardiomyopathy.
|
| 巻・号 |
289(5)
|
| ページ |
H1858-64
|
| 公開日 |
2005-11-1
|
| DOI |
10.1152/ajpheart.00216.2005
|
| PII |
00216.2005
|
| PMID |
15937097
|
| MeSH |
Animals
Cardiomyopathies / chemically induced*
Cardiomyopathies / pathology*
Cardiomyopathies / physiopathology
Cytokines / biosynthesis
Cytokines / genetics
Cytokines / pharmacology*
Electrocardiography
Female
Hemodynamics / physiology
Male
Matrix Metalloproteinase 2 / genetics*
Mice
Mice, Knockout
Myocarditis / pathology*
Myocarditis / physiopathology
Myocardium / pathology
Organ Size
RNA, Messenger / biosynthesis
RNA, Messenger / genetics
Survival Analysis
Tissue Inhibitor of Metalloproteinases / physiology
Tumor Necrosis Factor-alpha / metabolism
|
| IF |
3.864
|
| 引用数 |
35
|
|
WOS 分野
|
CARDIAC & CARDIOVASCULAR SYSTEMS
PHYSIOLOGY
PERIPHERAL VASCULAR DISEASE
|
| リソース情報 |
| 実験動物マウス |
RBRC00398 |
