title: Inhibition of PTEN expression and activity by angiotensin II induces proliferation and migration of vascular smooth muscle cells.
abstract: PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor and has been suggested recently to be involved in the regulation of cardiovascular diseases. The molecular mechanisms of this regulation are however poorly understood. This study shows that down regulation of PTEN expression and activity by angiotensin II (Ang II) increased proliferation and migration of vascular smooth muscle cells (VSMCs). The presence of Ang II induced rapid PTEN phosphorylation and oxidation in accordance with increased AKT and FAK phosphorylation. The Ang II-mediated VSMC proliferation and migration was inhibited when cellular PTEN expression was increased by AT1 inhibitor losartan, PPARγ agonist rosiglitazone, NF-κB inhibitor BAY 11-7082. Over expression of PTEN in VSMCs by adenovirus transduction also resulted in inhibition of cell proliferation and migration in response to Ang II. These results suggest that PTEN down-regulation is involved in proliferation and migration of VSMCs induced by Ang II. This provides insight into the molecular regulation of PTEN in vascular smooth muscle cells and suggests that targeting the action of PTEN may represent an effective therapeutic approach for the treatment of cardiovascular diseases.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Dong
authors.forename: Lu-Gang
authors.initials: LG
authors.lastname: Yu
authors.forename: Rong
authors.initials: R
authors.lastname: Sun
authors.forename: Yan-Na
authors.initials: YN
authors.lastname: Cheng
authors.forename: Hua
authors.initials: H
authors.lastname: Cao
authors.forename: Kang-Min
authors.initials: KM
authors.lastname: Yang
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Dong
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Guo
mesh_terms: D000256:Adenoviridae; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D046509:Tissue Culture Techniques; D014161:Transduction, Genetic; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D047228:Angiotensin II Type 1 Receptor Blockers; D009570:Nitriles; D013450:Sulfones; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D000804:Angiotensin II; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; D019808:Losartan