Department of Microbiology, and Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
Korean J Physiol Pharmacol. 2009 Oct;13(5):385-92. doi: 10.4196/kjpp.2009.13.5.385. Epub 2009 Oct 31.
Angiotensin II (Ang II) plays an important role in vascular hypertension. The role of the chemokine CCL5 on Ang II-induced activities in vascular smooth muscle cells (VSMCs) has not been studied. In this study, we elucidated the effect of CCL5 on Ang II-induced 12-lipoxygenase (LO) expression and cell proliferation in spontaneously hypertensive rats (SHR) VSMCs. CCL5 decreased Ang II-induced 12-LO mRNA expression and protein production, and it increased Ang II type 2 (AT(2)) receptor expression in SHR VSMCs. The inhibitory effect of CCL5 on Ang II-induced 12-LO mRNA expression was mediated through the AT(2) receptor. Although treatment of CCL5 alone induced SHR VSMCs proliferation, CCL5 inhibited Ang II-induced VSMCs proliferation and PD123,319, an AT(2) receptor antagonist, blocked the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation. Phosphorylation of p38 was detected in VSMCs treated with Ang II or CCL5 alone. But, decrease of p38 phosphorylation was detected in VSMCs treated with Ang II and CCL5 simultaneously (Ang II/CCL5) and PD123,319 increased p38 phosphorylation in VSMCs treated with Ang II/CCL5. Therefore, these results suggest that the inhibitory effect of CCL5 on Ang II-induced VSMCs proliferation is mediated by the AT(2) receptor via p38 inactivation, and CCL5 may play a beneficial role in Ang II-induced vascular hypertension.
血管紧张素 II（Ang II）在血管高血压中起着重要作用。趋化因子 CCL5 在血管平滑肌细胞（VSMCs）中对 Ang II 诱导的活性的作用尚未研究。在这项研究中，我们阐明了 CCL5 在 Ang II 诱导的自发性高血压大鼠（SHR）VSMCs 中 12-脂氧合酶（LO）表达和细胞增殖中的作用。CCL5 降低了 Ang II 诱导的 12-LO mRNA 表达和蛋白产生，并增加了 SHR VSMCs 中的 Ang II 型 2（AT（2））受体表达。CCL5 对 Ang II 诱导的 12-LO mRNA 表达的抑制作用是通过 AT（2）受体介导的。虽然 CCL5 单独处理诱导了 SHR VSMCs 的增殖，但 CCL5 抑制了 Ang II 诱导的 VSMCs 增殖，而 PD123,319，一种 AT（2）受体拮抗剂，阻断了 CCL5 对 Ang II 诱导的 VSMCs 增殖的抑制作用。在单独用 Ang II 或 CCL5 处理的 VSMCs 中检测到 p38 的磷酸化。但是，在同时用 Ang II 和 CCL5 处理的 VSMCs 中检测到 p38 磷酸化的减少（Ang II/CCL5），而 PD123,319 增加了 Ang II/CCL5 处理的 VSMCs 中的 p38 磷酸化。因此，这些结果表明，CCL5 对 Ang II 诱导的 VSMCs 增殖的抑制作用是通过 AT（2）受体通过 p38 失活介导的，CCL5 可能在 Ang II 诱导的血管高血压中发挥有益作用。
