TNF-α and myocardial matrix metalloproteinases in heart failure:: relationship to LV remodeling
TNF-α and myocardial matrix metalloproteinases in heart failure:: relationship to LV remodeling
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DOI：
10.1152/ajpheart.00526.2001
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发表时间：
2002-04-01
影响因子：
4.8
通讯作者：
Spinale, FG
中科院分区：
文献类型：
--
作者：
Bradham, WS;Moe, G;Spinale, FG
细胞因子肿瘤坏死因子（TNF）-α与左心室（LV）重塑有因果关系，但这种作用的分子基础尚不清楚。基质金属蛋白酶（MMP）参与心脏重塑，并可由TNF-α调节。本研究验证了中心假设，即给予TNF-α阻断蛋白可阻止MMP的诱导并改变LV衰竭中心肌重塑的过程。成年犬随机分为以下几组：1）慢性起搏（250次/分，28天，n = 12），2）慢性起搏，同时给予TNF-α阻断蛋白（TNF阻断）使用可溶性p75 TNF受体融合蛋白（TNFR：Fc;以0.5mg/kg每周两次皮下施用，n = 7）和3）正常对照（n = 10）。慢性起搏组左室舒张末期容积较对照组增加（83 +/- vs. 118 +/- ml，P
The cytokine tumor necrosis factor (TNF)-alpha has been causally linked to left ventricular (LV) remodeling, but the molecular basis for this effect is unknown. Matrix metalloproteinases (MMPs) have been implicated in cardiac remodeling and can be regulated by TNF-alpha. This study tested the central hypothesis that administration of a TNF-alpha blocking protein would prevent the induction of MMPs and alter the course of myocardial remodeling in developing LV failure. Adult dogs were randomly assigned to the following groups: 1) chronic pacing (250 beats/min, 28 days, n = 12), 2) chronic pacing with concomitant administration of a TNF-alpha blocking protein (TNF block) using a soluble p75 TNF receptor fusion protein (TNFR: Fc; administered at 0.5 mg/kg twice a week subcutaneously, n = 7), and 3) normal controls (n = 10). LV end-diastolic volume increased from control with chronic pacing (83 +/- vs. 118 +/- ml, P