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http://dx.doi.org/10.4196/kjpp.2009.13.5.385

Downregulation of Angiotensin II-Induced 12-Lipoxygenase Expression and Cell Proliferation in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats by CCL5  

Kim, Jung-Hae (Department of Microbiology, and Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University)
Kim, Hee-Sun (Department of Microbiology, and Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.13, no.5, 2009 , pp. 385-392 More about this Journal
Abstract
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.
Keywords
Angiotensin II; Angiotensin II type 2 receptor; Cell proliferation; Chemokine CCL5; 12-lipoxygenase;
Citations & Related Records
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