title: Angiotensin II inhibits chemokine CCL5 expression in vascular smooth muscle cells from spontaneously hypertensive rats.
abstract: Angiotensin II (Ang II) exerts some of its effects on the vasculature by stimulating chemokines and 12-lipoxygenase (12-LO). In addition, a high expression of chemokines by Ang II has been observed in vascular smooth muscle cells (VSMCs) in spontaneously hypertensive rats (SHR). In this study, the action mechanism of Ang II on CCL5 expression in SHR VSMCs was examined. Expression of CCL5 in SHR thoracic aorta tissues and VSMCs was lower than that in normotensive Wistar-Kyoto rats (WKY) thoracic aorta tissues and VSMCs. Moreover, Ang II inhibited CCL5 expression in SHR VSMCs, but not in WKY VSMCs. Inhibition of CCL5 by Ang II was mediated by both Ang II subtype 1 receptor (AT(1)R) and subtype 2 receptor (AT(2)R) activation in SHR VSMCs. However, Ang II did not inhibit CCL5 expression in SHR VSMCs that were transfected with 12-LO small interfering RNA. In addition, 12-LO metabolite, 12(S)-hydroxyeicosatetraenoic acid (HETE) inhibited CCL5 mRNA expression in SHR VSMCs. The expression of Ang II-induced 12-LO was also blocked by both AT(1)R and AT(2)R inhibitors. Mitogen-activated protein (MAP) kinase, extracellular signal-regulated kinase (ERK)1/2, p38 and Jun N-terminal kinase pathways all mediated the inhibitory action of Ang II on CCL5 expression in SHR VSMCs. Taken together, the inhibitory action of Ang II on CCL5 expression was shown to be mediated by the 12-LO pathway through the activation of both of AT(1)R and AT(2)R and this process was associated with MAP kinase pathways in SHR VSMCs. This result suggests that upregulation of 12-LO by Ang II leads to the downregulation of CCL5 expression in SHR VSMCs.
authors.affiliation: Department of Emergency Medicine, College of Medicine, Dong-A University, Pusan, South Korea.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yun
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Byung Soo
authors.initials: BS
authors.lastname: Do
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D024202:Electrophoretic Mobility Shift Assay; D007150:Immunohistochemistry; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D018946:Chemokine CCL5; D034741:RNA, Small Interfering; D000804:Angiotensin II; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D012313:RNA; D001092:Arachidonate 12-Lipoxygenase; D020928:Mitogen-Activated Protein Kinases