首页> 外文期刊>American Journal of Physiology >Assembly, activation, and signaling by kinin-forming proteins on human vascular smooth muscle cells.
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Assembly, activation, and signaling by kinin-forming proteins on human vascular smooth muscle cells.

机译:激肽形成蛋白在人血管平滑肌细胞上的组装,激活和信号传导。

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摘要

Cardiovascular disease is the number one cause of death in the United States. Vascular smooth muscle cells (VSMC) are an important constituent of the vessel wall that can bring about pathological changes leading to vascular disease. Depending on the environment, the function of VSMC can deviate profoundly from its normal contractile role. Despite advances in research, the underlying mechanisms that activate VSMC toward vascular disease are poorly understood. For the first time, we have observed that factor XII and high-molecular-weight kininogen, constituents of the blood plasma, can bind to VSMC in a Zn2+-dependent manner. In the presence of prekallikrein, this assembly of factor XII and high-molecular-weight kininogen on VSMC leads to the activation of prekallikrein to kallikrein with a rapid formation of bradykinin. The amount of bradykinin in the culture medium then decreases, presumably because of the presence of a kininase activity. p44/42 mitogen-activated protein kinase is rapidly phosphorylated in response to in situ-generated or in vitro-added bradykinin and is inhibited by bradykinin antagonist HOE-140. Binding of factor XII to VSMC also results in a concentration-dependent phosphorylation of p44/42 mitogen-activated protein kinase. This early mitogenic signal, which is also implicated in atherogenesis, may change the metabolic and proliferative activity of VSMC, which are key steps in the progression of atherosclerosis.
机译:在美国,心血管疾病是第一大死亡原因。血管平滑肌细胞(VSMC)是血管壁的重要组成部分,可引起导致血管疾病的病理变化。根据环境的不同,VSMC的功能可能会大大偏离其正常的收缩作用。尽管研究取得了进展,但激活VSMC导致血管疾病的潜在机制知之甚少。首次,我们发现血浆XII因子和高分子量激肽原可以以Zn2 +依赖的方式与VSMC结合。在前激肽释放酶的存在下,VSMC上的因子XII和高分子量激肽原的这种组装导致前激肽释放酶活化为激肽释放酶,并迅速形成了缓激肽。然后,培养基中缓激肽的量减少,大概是由于激肽酶活性的存在。 p44 / 42丝裂原活化蛋白激酶响应于原位生成的或体外添加的缓激肽而迅速磷酸化,并被缓激肽拮抗剂HOE-140抑制。因子XII与VSMC的结合还导致p44 / 42丝裂原活化蛋白激酶的浓度依赖性磷酸化。这种早期有丝分裂信号也与动脉粥样硬化有关,它可能会改变VSMC的代谢和增殖活性,这是动脉粥样硬化进展的关键步骤。

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