Effect of CCL5 on dimethylarginine dimethylaminohydrolase-1 production in vascular smooth muscle cells from spontaneously hypertensive rats

Title
Effect of CCL5 on dimethylarginine dimethylaminohydrolase-1 production in vascular smooth muscle cells from spontaneously hypertensive rats
Author(s)
김희선김혜영김정혜
Keywords
ANGIOTENSIN-II RECEPTOR; ASYMMETRIC DIMETHYLARGININE; EXPRESSION; RANTES; INFLAMMATION; DYSFUNCTION; MONOCYTES
Issue Date
201310
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Citation
CYTOKINE, v.64, no.1, pp.227 - 233
Abstract
Chemokines promote vascular inflammation and play a pathogenic role in the development and maintenance of hypertension. However, in our previous study, chemokine CCL5 was shown to reduce Ang II-induced 12-lipoxygenase (12-LO) production as well as proliferation in vascular smooth muscle cells (VSMCs) obtained from spontaneously hypertensive rats (SHR). Dimethylarginine dimethylaminohydrolase (DDAH) acts as an important regulator of vascular function by metabolizing and regulating plasma asymmetric (N-G,N-G) dimethylarginine (ADMA), a major risk factor for cardiovascular disease. Therefore, in this study, we investigated the effect of CCL5 on DDAH-1 production in SHR VSMCs. Constitutive expression of DDAH-1 in VSMCs from SHR was higher than that in VSMCs from normotensive Wistar Kyoto rats (WRY), whereas expression of DDAH-2 was not significantly different between SHR and WRY VSMCs. CCL5 increased DDAH-1 production and attenuated Ang II-induced DDAH-1 inhibition in SHR VSMCs. In addition, although CCL5 did not affect the level of asymmetric (N-G,N-G) dimethylarginine (ADMA), it attenuated Ang II-induced ADMA production through DDAH-1 activity. DDAH-1 induction by CCL5 was mediated by the Ang II subtype 2 receptor (AT(2) R) pathway. Further, attenuation of Ang II-induced 12-LO and endothelin-1 (ET-1) expression by CCL5 could be attributed to DDAH-1 activity. These findings combined with our previous results suggest that CCL5 is a potential down-regulatory factor in Ang II-induced vascular hypertension. (C) 2013 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/28841http://dx.doi.org/10.1016/j.cyto.2013.06.316
ISSN
1043-4666
Appears in Collections:
의과대학 > 미생물학교실 > Articles
의과대학 > 영상의학과학교실 > Articles
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