Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5898658 | Cytokine | 2008 | 11 Pages |
Abstract
Asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor, is also an important inflammatory factor contributing to the development of atherosclerosis (AS). The present study was to test the effect of ADMA on angiotensin (Ang) II-induced monocytic adhesion. Human monocytoid cells (THP-1) or isolated peripheral blood monocyte cells (PBMCs) were incubated with Ang II (10â6 M) or exogenous ADMA (30 μM) for 4 or 24 h in the absence or presence of losartan or antioxidant PDTC. In cultured THP-1 cells, Ang II (10â6 M) for 24 h elevated the level of ADMA in the medium, upregulated the protein expression of protein arginine methyltransferase (PRMT) and decreased the activity of dimethylarginine dimethylaminohydrolase (DDAH). Both of Ang II and ADMA increased monocytic adhesion to human umbilical vein endothelial cells (HUVECs), elevated the levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 and tumor necrosis factor (TNF)-α and upregulated CCR2 and CXCR2 mRNA expression, concomitantly with increase in reactive oxygen species (ROS) generation and activation of nuclear factor (NF)-κB. Pretreatment with losartan (10 μM) or PDTC (10 μM) abolished the effects mediated by Ang II or ADMA. In isolated PBMCs from healthy individuals, ADMA upregulated the expression of CXCR2 mRNA, which was attenuated by losartan (10 μM), however, ADMA had no effect on surface protein expression of CCR2. The present results suggest that ADMA may be involved in monocytic adhesion induced by Ang II via activation of chemokine receptors by ROS/NF-κB pathway.
Keywords
THP-1PRMTsNF-κβIL-8DDAHARBMCP-1HUVECiNOSICAM-1ADMAROSAtherosclerosisAngiotensin II (Ang II)Angiotensin IIInterleukin-8Ang IIDimethylarginine dimethylaminohydrolaseasymmetric dimethylarginineAsymmetric dimethylarginine (ADMA)inducible nitric oxide synthaseTNF-αnuclear factor kappaBAngiotensin receptor blockerACEI یا angiotensin convert enzyme inhibitorangiotensin-converting enzyme inhibitorintercellular adhesion moleculemonocyte chemoattractant protein-1high performance liquid chromatographyHPLCChemokineReactive oxygen species
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Authors
Meifang Chen, Yuanjian Li, Tianlun Yang, Yongjin Wang, Yongping Bai, Xiumei Xie,