Christopher J, Velarde V, Jaffa A A
Department of Medicine, Medical University of South Carolina, Charleston, USA.
Hypertension. 2001 Sep;38(3 Pt 2):602-5. doi: 10.1161/01.hyp.38.3.602.
Vascular smooth muscle cell (VSMC) proliferation is a prominent feature of the atherosclerotic process that occurs after endothelial injury. Although a vascular wall kallikrein-kinin system has been described, its contribution to vascular disease remains undefined. Because the B(1)-kinin receptor subtype (B1KR) is induced in VSMCs only in response to injury, we hypothesize that this receptor may be mediating critical events in the progression of vascular disease. In the present study, we provide evidence that des-Arg(9)-bradykinin (dABK) (10(-8) M), acting through B1KR, stimulates the phosphorylation of mitogen-activated protein kinase (MAPK) (p42(mapk) and p44(mapk)). Activation of MAPK by dABK is mediated via a cholera toxin-sensitive pathway and appears to involve protein kinase C, Src kinase, and MAPK kinase. These findings demonstrate that the activation of B1KR in VSMCs leads to the generation of second messengers that converge to activate MAPK and provide a rationale to investigate the mitogenic actions of dABK in vascular injury.
血管平滑肌细胞（VSMC）增殖是内皮损伤后发生的动脉粥样硬化过程的一个显著特征。尽管已经描述了血管壁激肽释放酶-激肽系统，但其对血管疾病的作用仍不明确。由于B（1）-激肽受体亚型（B1KR）仅在VSMC中因损伤而被诱导，我们推测该受体可能介导血管疾病进展中的关键事件。在本研究中，我们提供证据表明，通过B1KR起作用的去-精氨酸（9）-缓激肽（dABK）（10^-8 M）刺激丝裂原活化蛋白激酶（MAPK）（p42(mapk)和p44(mapk)）的磷酸化。dABK对MAPK的激活是通过霍乱毒素敏感途径介导的，似乎涉及蛋白激酶C、Src激酶和MAPK激酶。这些发现表明，VSMC中B1KR的激活导致第二信使的产生，这些第二信使汇聚以激活MAPK，并为研究dABK在血管损伤中的促有丝分裂作用提供了理论依据。
