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首页> 外文期刊>Journal of Cellular Physiology >Modulation of vascular endothelial cell senescence by integrin beta4.
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Modulation of vascular endothelial cell senescence by integrin beta4.

机译:调制的血管内皮细胞衰老通过整合素beta4。

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Increasing evidence has demonstrated that the senescence of vascular endothelial cells (VECs) has critical roles in the pathogenesis of vascular dysfunction. Finding important factors that regulate VEC senescence will help provide novel therapeutic strategies for vascular disorders. Previously, we found that integrin beta4 was involved in VEC senescence. However, the mechanism underlying VEC senescence mediated by integrin beta4 remains poorly understand. In this study, we used a mouse in vivo model and showed that the level of integrin beta4 in the endothelium of mouse thoracic aorta was increased during natural aging and atherosclerosis. Furthermore, we found that H-ras, caveolin-1, and AP-1 were implicated in the senescent signal pathway mediated by integrin beta4 in human umbilical vein ECs (HUVECs). Knockdown of integrin beta4 could attenuate HUVEC senescent features, including increased interleukin-8 (IL-8) release and decreased endothelial nitric oxide synthase (eNOS) and NO levels and mitochondrial membrane potential in vitro. Our findings provide new clues illustrating the mechanism of VEC senescence. Integrin beta4 might be a potential target for therapy in cardiovascular diseases.
机译:越来越多的证据证明了衰老的血管内皮细胞(vec)发病机理的关键作用血管功能障碍。VEC衰老调节将帮助提供血管的新治疗策略障碍。beta4参与VEC衰老。VEC衰老机制介导通过整合素beta4仍然缺乏了解。本研究中,我们使用一个鼠标和体内模型表明,整合素的水平beta4增加了对大鼠胸主动脉内皮在自然老化和动脉粥样硬化。此外,我们发现,h - caveolin-1,AP-1卷入其中衰老的信号通路由整合素beta4在人类脐静脉ECs (HUVECs)。整合素beta4可以减弱HUVEC衰老功能,包括interleukin-8增加(引发)释放和减少内皮氮氧化合成酶(以挪士),没有水平,线粒体膜电位体外。说明了研究提供新的线索VEC衰老的机制。是一个潜在的治疗目标心血管疾病。

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