title: Angiotensin II upregulates the expression of placental growth factor in human vascular endothelial cells and smooth muscle cells.
abstract: BACKGROUND
  Atherosclerosis is now recognized as a chronic inflammatory disease. Angiotensin II (Ang II) is a critical factor in inflammatory responses, which promotes the pathogenesis of atherosclerosis. Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family cytokines and is associated with inflammatory progress of atherosclerosis. However, the potential link between PlGF and Ang II has not been investigated. In the current study, whether Ang II could regulate PlGF expression, and the effect of PlGF on cell proliferation, was investigated in human vascular endothelial cells (VECs) and smooth muscle cells (VSMCs).
  
  
  RESULTS
  In growth-arrested human VECs and VSMCs, Ang II induced PlGF mRNA expression after 4 hour treatment, and peaked at 24 hours. 10-6 mol/L Ang II increased PlGF protein production after 8 hour treatment, and peaked at 24 hours. Stimulation with Ang II also induced mRNA expression of VEGF receptor-1 and -2(VEGFR-1 and -2) in these cells. The Ang II type I receptor (AT1R) antagonist blocked Ang II-induced PlGF gene expression and protein production. Several intracellular signals elicited by Ang II were involved in PlGF synthesis, including activation of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2) and PI3-kinase. A neutralizing antibody against PlGF partially inhibited the Ang II-induced proliferation of VECs and VSMCs. However, this antibody showed little effect on the basal proliferation in these cells, whereas blocking antibody of VEGF could suppress both basal and Ang II-induced proliferation in VECs and VSMCs.
  
  
  CONCLUSIONS
  Our results showed for the first time that Ang II could induce the gene expression and protein production of PlGF in VECs and VSMCs, which might play an important role in the pathogenesis of vascular inflammation and atherosclerosis.
authors.affiliation: Laboratory of Cardiovascular Diseases, National Key Laboratory of Biotherapy of Human Diseases, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Pingxi
authors.initials: P
authors.lastname: Pan
authors.forename: Hua
authors.initials: H
authors.lastname: Fu
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.forename: Fengming
authors.initials: F
authors.lastname: Luo
authors.forename: Wenchao
authors.initials: W
authors.lastname: Wu
authors.forename: Yingqiang
authors.initials: Y
authors.lastname: Guo
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D019138:Antibodies, Blocking / Q000494:pharmacology; D050197:Atherosclerosis; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D019138:Antibodies, Blocking; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000804:Angiotensin II; D000072483:Placenta Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D011493:Protein Kinase C; D048052:Mitogen-Activated Protein Kinase 3