Pollutant particles produce vasoconstriction and enhance MAPK signaling via angiotensin type I receptor.
Pollutant particles produce vasoconstriction and enhance MAPK signaling via angiotensin type I receptor.
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DOI：
10.1289/ehp.7736
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发表时间：
2005-08
影响因子：
10.4
通讯作者：
Huang, Yuh-Chin T
中科院分区：
文献类型：
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作者：
Li, Zhuowei;Carter, Jacqueline D;Dailey, Lisa A;Huang, Yuh-Chin T
暴露于颗粒物(PM)与急性心血管死亡和发病率有关，但其机制尚不完全清楚。在这项研究中，我们假设PM可能激活血管紧张素1型受体(AT1R)，这是一种G蛋白偶联受体，调节炎症和血管功能。我们研究了密苏里州圣路易斯城市颗粒物(UPS；标准参考物质1648)在使用或不使用AT1R拮抗剂氯沙坦的情况下，对离体大鼠肺动脉环收缩以及人肺动脉内皮细胞细胞外信号调节激酶1和2(ERK1/2)和p38丝裂原激活蛋白激酶(MAPKs)的急性影响。1~100μg/mLUPS可引起大鼠急性肺动脉收缩。UPS还呈时间和剂量依赖性地增加ERK1/2和p38MAPK的磷酸化。氯沙坦可抑制血管收缩，抑制ERK1/2和p38的激活。UPS的水溶性部分足以诱导ERK1/2和p38的磷酸化，这也是氯沙坦可抑制的。UPS中含有的两种可溶性过渡金属铜和钒可引起肺血管收缩和ERK1/2和p38的磷酸化，而氯沙坦仅抑制p38的磷酸化。血管紧张素转换酶抑制剂卡托普利可减弱上调诱导的ERK1/2和p38的激活。这些结果表明局部肾素-血管紧张素系统的激活可能在PM引起的心血管效应中起重要作用。
Exposure to particulate matter (PM) is associated with acute cardiovascular mortality and morbidity, but the mechanisms are not entirely clear. In this study, we hypothesized that PM may activate the angiotensin type 1 receptor (AT1R), a G protein-coupled receptor that regulates inflammation and vascular function. We investigated the acute effects of St. Louis, Missouri, urban particles (UPs; Standard Reference Material 1648) on the constriction of isolated rat pulmonary artery rings and the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) in human pulmonary artery endothelial cells with or without losartan, an antagonist of AT1R. UPs at 1–100 μg/mL induced acute vaso-constriction in pulmonary artery. UPs also produced a time- and dose-dependent increase in phosphorylation of ERK1/2 and p38 MAPK. Losartan pretreatment inhibited both the vasoconstriction and the activation of ERK1/2 and p38. The water-soluble fraction of UPs was sufficient for inducing ERK1/2 and p38 phosphorylation, which was also losartan inhibitable. Copper and vanadium, two soluble transition metals contained in UPs, induced pulmonary vasoconstriction and phosphorylation of ERK1/2 and p38, but only the phosphorylation of p38 was inhibited by losartan. The UP-induced activation of ERK1/2 and p38 was attenuated by captopril, an angiotensin-converting enzyme inhibitor. These results indicate that activation of the local renin–angiotensin system may play an important role in cardiovascular effects induced by PM.