Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells.
Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells.
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DOI：
10.1161/01.res.83.9.952
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发表时间：
1998-11
影响因子：
20.1
通讯作者：
Xi-lin Chen;P. Tummala;M. Olbrych;R. Alexander;R. Medford
中科院分区：
文献类型：
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作者：
Xi-lin Chen;P. Tummala;M. Olbrych;R. Alexander;R. Medford
单核细胞向血管壁的浸润是动脉粥样硬化过程中的关键起始步骤，其部分由单核细胞趋化蛋白-1（MCP-1）介导。高血压，特别是在存在激活的肾素-血管紧张素系统的情况下，是动脉粥样硬化发展的主要危险因素。为了探讨高血压和动脉粥样硬化之间联系的潜在分子基础，我们研究了血管紧张素II（Ang II）对大鼠主动脉平滑肌细胞MCP-1基因表达的影响。血管紧张素Ⅱ处理的大鼠平滑肌细胞MCP-1 mRNA积累呈剂量依赖性增加，而AT 1受体拮抗剂氯沙坦可阻止这种增加。Ang Ⅱ还激活MCP-1基因转录。抑制NADH/NADPH氧化酶，产生超氧化物和H2 O2，与二苯碘鎓或夹竹桃素减少血管紧张素II诱导的MCP-1 mRNA的积累。过氧化氢酶抑制血管紧张素II诱导MCP-1基因表达，提示H2 O2的第二信使作用。酪氨酸激酶抑制剂genistein和丝裂原活化蛋白激酶抑制剂PD 098059抑制Ang II诱导的MCP-1基因表达，与丝裂原活化蛋白激酶依赖的信号传导机制一致。因此，血管紧张素II可能通过直接激活血管平滑肌细胞中MCP-1基因的表达而促进动脉粥样硬化的形成。
Monocyte infiltration into the vessel wall, a key initial step in the process of atherosclerosis, is mediated in part by monocyte chemoattractant protein-1 (MCP-1). Hypertension, particularly in the presence of an activated renin-angiotensin system, is a major risk factor for the development of atherosclerosis. To investigate a potential molecular basis for a link between hypertension and atherosclerosis, we studied the effects of angiotensin II (Ang II) on MCP-1 gene expression in rat aortic smooth muscle cells. Rat smooth muscle cells treated with Ang II exhibited a dose-dependent increase in MCP-1 mRNA accumulation that was prevented by the AT1 receptor antagonist losartan. Ang II also activated MCP-1 gene transcription. Inhibition of NADH/NADPH oxidase, which generates superoxide and H2O2, with diphenylene iodonium or apocynin decreased Ang II-induced MCP-1 mRNA accumulation. Induction of MCP-1 gene expression by Ang II was inhibited by catalase, suggesting a second messenger role for H2O2. The tyrosine kinase inhibitor genistein and the mitogen-activated protein kinase kinase inhibitor PD098059 inhibited Ang II-induced MCP-1 gene expression, consistent with a mitogen-activated protein kinase-dependent signaling mechanism. Ang II may thus promote atherogenesis by direct activation of MCP-1 gene expression in vascular smooth muscle cells.