title: iPLA2β overexpression in smooth muscle exacerbates angiotensin II-induced hypertension and vascular remodeling.
abstract: OBJECTIVE
  Calcium independent group VIA phospholipase A(2) (iPLA(2)β) is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA(2)β affects vascular morphology and blood pressure is unknown. The current study addresses this question by evaluating the basal- and angiotensin II infusion-induced vascular remodeling and hypertension in smooth muscle specific iPLA(2)β transgenic (iPLA(2)β-Tg) mice.
  
  
  RESULTS
  Blood pressure was monitored by radiotelemetry and vascular remodeling was assessed by morphologic analysis. We found that the angiotensin II-induced increase in diastolic pressure was significantly higher in iPLA(2)β-Tg than iPLA(2)β-Wt mice, whereas, the basal blood pressure was not significantly different. The media thickness and media∶lumen ratio of the mesenteric arteries were significantly increased in angiotensin II-infused iPLA(2)β-Tg mice. Analysis revealed no difference in vascular smooth muscle cell proliferation. In contrast, adenovirus-mediated iPLA(2)β overexpression in cultured vascular smooth muscle cells promoted angiotensin II-induced [(3)H]-leucine incorporation, indicating enhanced hypertrophy. Moreover, angiotensin II infusion-induced c-Jun phosphorylation in vascular smooth muscle cells overexpressing iPLA2β to higher levels, which was abolished by inhibition of 12/15 lipoxygenase. In addition, we found that angiotensin II up-regulated the endogenous iPLA(2)β protein in-vitro and in-vivo.
  
  
  CONCLUSIONS
  The present study reports that iPLA(2)β up-regulation exacerbates angiotensin II-induced vascular smooth muscle cell hypertrophy, vascular remodeling and hypertension via the 12/15 lipoxygenase and c-Jun pathways.
authors.affiliation: Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Calderon
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Su
authors.forename: Zhongwen
authors.initials: Z
authors.lastname: Xie
authors.forename: Zhenheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Wanda
authors.initials: W
authors.lastname: Eberhard
authors.forename: Ming C
authors.initials: MC
authors.lastname: Gong
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001093:Arachidonate 15-Lipoxygenase; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003971:Diastole / Q000187:drug effects; D054522:Group VI Phospholipases A2 / Q000378:metabolism*; D006973:Hypertension / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D006984:Hypertrophy; D007930:Leucine / Q000378:metabolism; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D000804:Angiotensin II; D016718:Arachidonic Acid; D001093:Arachidonate 15-Lipoxygenase; D048051:p38 Mitogen-Activated Protein Kinases; D054522:Group VI Phospholipases A2; C516476:Pla2g6 protein, mouse; D007930:Leucine