Deficiency of TIMP-1 exacerbates LV remodeling after myocardial infarction in mice
Deficiency of TIMP-1 exacerbates LV remodeling after myocardial infarction in mice
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DOI：
10.1152/ajpheart.00511.2002
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发表时间：
2003-01-01
影响因子：
4.8
通讯作者：
Spinale, FG
中科院分区：
文献类型：
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作者：
Creemers, EEJM;Davis, JN;Spinale, FG
最近的研究已经针对通过抑制活化的基质金属蛋白酶（MMPs）来调节心力衰竭过程。我们假设，MMP组织抑制剂（TIMP）-1缺乏导致MMP抑制控制的丧失改变了野生型（WT）和TIMP-1（-/-）小鼠梗死后心室重构和诱导慢性心肌梗死（MI）的过程。从WT和TIMP-1（-/-）小鼠获得的左心室（LV）压力-容积环证明LV舒张末期容积[52+/-4（WT）vs. 71+/-6（TIMP-1（-/-））穆尔]和左室舒张末期压[9.0+/-1.2（WT）vs. 12.7+/-1.4（TIMP-1（-/-））mmHg]在TIMP-1（-/-）小鼠中在MI后2 wk显著增加。心肌梗死后，WT组和TIMP-1（-/-）组的LV收缩力降低程度相似，如LV收缩末期压力-容积关系显著下降所示。TIMP-1（-/-）小鼠的心室重量和LV肌细胞的横截面积显著增加，表明肥大反应更明显。在TIMP-1（-/-）对照组中观察到的纤维胶原蛋白的显著损失可能是在TIMP-1（-/-）小鼠MI后观察到的LV改变的重要促成因素。这些研究结果表明，TIMP-1缺乏会加剧小鼠MI后的不良LV重塑，并强调了TIMP-1对心脏MMP活性的局部内源性控制的重要性。
Recent studies have been directed at modulating the heart failure process through inhibition of activated matrix metalloproteinases (MMPs). We hypothesized that a loss of MMP inhibitory control by tissue inhibitor of MMP (TIMP)-1 deficiency alters the course of postinfarction chamber remodeling and induced chronic myocardial infarction (MI) in wild-type (WT) and TIMP-1(-/-) mice. Left ventricular (LV) pressure-volume loops obtained from WT and TIMP-1(-/-) mice demonstrated that LV end-diastolic volume [52+/-4 (WT) vs. 71+/-6 (TIMP-1(-/-)) mul] and LV end-diastolic pressure [9.0+/-1.2 (WT) vs. 12.7+/-1.4 (TIMP-1(-/-)) mmHg] were significantly increased in the TIMP-1(-/-) mice 2 wk after MI. LV contractility was reduced to a similar degree in the WT and TIMP-1(-/-) groups after MI, as indicated by a significant fall in the LV end-systolic pressure-volume relationship. Ventricular weight and cross-sectional areas of LV myocytes were significantly increased in TIMP-1(-/-) mice, indicating that the hypertrophic response was more pronounced. The observed significant loss of fibrillar collagen in the TIMP-1(-/-) controls may have been an important contributory factor for the observed LV alterations in the TIMP-1(-/-) mice after MI. These findings demonstrate that TIMP-1 deficiency amplifies adverse LV remodeling after MI in mice and emphasizes the importance of local endogenous control of cardiac MMP activity by TIMP-1.