title: Angiotensin-(1-7) Attenuates Angiotensin II-Induced ICAM-1, VCAM-1, and MCP-1 Expression via the MAS Receptor Through Suppression of P38 and NF-κB Pathways in HUVECs.
abstract: OBJECTIVE
  Atherosclerosis is a chronic inflammatory disease. Intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) play important roles in inflammatory processes. P38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling regulate ICAM-1, VCAM-1, and MCP-1 expression. Angiotensin (Ang) II upregulates ICAM-1, VCAM-1, and MCP-1 expression through the P38 MAPK and NF-κB pathways. Ang-(1-7) may oppose the actions of Ang II. We investigated whether Ang-(1-7) prevents Ang II-induced ICAM-1, VCAM-1, and MCP-1 expression in human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  ICAM-1, VCAM-1, and MCP-1 expression was estimated by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA); P38, NF-κB, and p-IκB-α expression was estimated by western blotting.
  
  
  RESULTS
  Ang-(1-7) inhibited Ang II-induced ICAM-1, VCAM-1, and MCP-1 expression and secretion in HUVECs. Ang II sharply increased P38 MAPK phosphorylation, which was inhibited by pretreatment with Ang-(1-7). Moreover, Ang-(1-7) significantly inhibited Ang II-induced IκB-α phosphorylation and NF-κB P65 nuclear translocation. The MAS receptor antagonist A-779 abolished the suppressive effects of Ang-(1-7).
  
  
  CONCLUSIONS
  Ang-(1-7) attenuates Ang II-induced ICAM-1, VCAM-1, and MCP-1 expression via the MAs receptor by suppressing the P38 and NF-κB pathways in HUVECs. Ang-(1-7) might delay the progression of inflammatory diseases, including atherosclerosis.
authors.affiliation: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Nana
authors.initials: N
authors.lastname: Zhang
authors.forename: Huiyu
authors.initials: H
authors.lastname: Yang
authors.forename: Rui
authors.initials: R
authors.lastname: Bai
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Bian
authors.forename: Chuanshi
authors.initials: C
authors.lastname: Xiao
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D000803:Angiotensin I; D048051:p38 Mitogen-Activated Protein Kinases; C118790:angiotensin I (1-7)