In rats decreased bioavailability of nitric oxide induces oxidative stress and right heart failure. Oxidative stress can activate matrix metalloproteinase-2 (MMP2). We addressed the question whether increasing oxidative defense by administration of the SOD mimetic Tempol or direct inhibition of MMP2 activity by SB-3CT mitigates right heart failure. Rats received l-NAME for four weeks and during week three and four treatment groups received either Tempol or SB-3CT in addition. After four weeks heart function was analyzed by echocardiography, organ weights and expression of NPPB and COL1A1 were analyzed, oxidative stress was monitored by DHE-staining and MMP2 activity was quantified by proteolytic auto-activation, zymography, and troponin I degradation. l-NAME induced oxidative stress and MMP2 activity stronger in the right ventricle than in the left ventricle. Troponin I, a MMP2 substrate, was degraded in right ventricles. Tempol reduced oxidative stress and preferentially affected the expression of fibrotic genes (i.e. COL1A1) and fibrosis. Tempol and SB-3CT mitigated right but not left ventricular hypertrophy. Neither SB-3CT nor Tempol alone strongly improved right ventricular function. In conclusion, both MMP2 activity and oxidative stress contribute to right ventricular failure but neither is MMP2 activation linked to oxidative stress nor does oxidative stress and MMP2 activity have common targets.

中文翻译：

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抑制 MMP2 活性可减轻 N-omega-硝基-L-精氨酸甲酯 (L-NAME) 诱导的右心衰竭


在大鼠中，一氧化氮生物利用度降低会诱发氧化应激和右心衰竭。氧化应激可以激活基质金属蛋白酶-2 (MMP2)。我们解决了通过施用 SOD 模拟物 Tempol 来增强氧化防御或通过 SB-3CT 直接抑制 MMP2 活性是否可以减轻右心衰竭的问题。大鼠接受 l-NAME 治疗 4 周，第三周和第四周治疗组还接受 Tempol 或 SB-3CT。四周后，通过超声心动图分析心脏功能，分析器官重量以及 NPPB 和 COL1A1 的表达，通过 DHE 染色监测氧化应激，并通过蛋白水解自动激活、酶谱和肌钙蛋白 I 降解来量化 MMP2 活性。 l-NAME 诱导的氧化应激和 MMP2 活性在右心室中比在左心室中更强。肌钙蛋白 I 是一种 MMP2 底物，在右心室中被降解。 Tempol 减少氧化应激并优先影响纤维化基因（即 COL1A1）和纤维化的表达。 Tempol 和 SB-3CT 可减轻右心室肥厚，但不能减轻左心室肥厚。单独使用 SB-3CT 或 Tempol 均不能显着改善右心室功能。总之，MMP2 活性和氧化应激都会导致右心室衰竭，但 MMP2 激活与氧化应激无关，氧化应激和 MMP2 活性也没有共同目标。