AVE 3085, a novel endothelial nitric oxide synthase enhancer, attenuates cardiac remodeling in mice through the Smad signaling pathway
AVE 3085, a novel endothelial nitric oxide synthase enhancer, attenuates cardiac remodeling in mice through the Smad signaling pathway
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AVE 3085 是一种新型内皮一氧化氮合酶增强剂，通过 Smad 信号通路减弱小鼠心脏重塑
DOI：
10.1016/j.abb.2015.02.020
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发表时间：
2015-03-15
影响因子：
3.9
通讯作者：
Dong, Yugang
中科院分区：
文献类型：
--
作者：
Chen, Yili;Chen, Cong;Dong, Yugang
AVE 3085是一种新的内皮型一氧化氮合酶增强剂。虽然AVE 3085治疗已被证明是有效的自发恢复高血压大鼠的内皮功能，很少有人知道AVE 3085的作用和机制，心脏重塑。本研究旨在研究AVE 3085对心脏重塑的影响以及该化合物作用的机制。对小鼠进行主动脉结扎以诱导心脏重塑，然后给予AVE 3085（10 mg/kg/天（-1），口服）4周。在治疗结束时，主动脉结扎治疗的小鼠表现出心脏重塑的显著升高，其特征在于左心室重量相对于体重增加，胶原沉积面积增加，平均肌细胞直径增加，以及肥大标志物心房利钠肽（ANP）和β-MHC的基因表达增加。这些指数在AVE 3085处理的小鼠中显著降低。此外，AVE 3085治疗降低了主动脉结扎治疗小鼠中Smad信号通路的表达和激活。我们的数据表明，AVE 3085减轻心脏重塑，这种作用可能是通过抑制Smad信号转导介导的。(C)2015 Elsevier Inc. All rights reserved.
AVE 3085 is a novel endothelial nitric oxide synthase enhancer. Although AVE 3085 treatment has been shown to be effective in spontaneously restoring endothelial function in hypertensive rats, little is known about the effects and mechanisms of AVE 3085 with respect to cardiac remodeling. The present study was designed to examine the effects of AVE 3085 on cardiac remodeling and the mechanisms underlying the effects of this compound. Mice were subjected to aortic banding to induce cardiac remodeling and were then administered AVE 3085 (10 mg kg day(-1), orally) for 4 weeks. At the end of the treatment, the aortic banding-treated mice exhibited significant elevations in cardiac remodeling, characterized by an increase in left ventricular weight relative to body weight, an increase in the area of collagen deposition, an increase in the mean myocyte diameter, and increases in the gene expressions of the hypertrophic markers atrial natriuretic peptide (ANP) and beta-MHC. These indexes were significantly decreased in the AVE 3085-treated mice. Furthermore, AVE 3085 treatment reduced the expression and activation of the Smad signaling pathway in the aortic banding-treated mice. Our data showed that AVE 3085 attenuated cardiac remodeling, and this effect was possibly mediated through the inhibition of Smad signaling. (C) 2015 Elsevier Inc. All rights reserved.