official journal of the American Association for Cancer Research 15: 53175322. 10 February 2012 | Volume 7 | Issue 2 | e31723 iPLA2b Overexpression in Smooth Muscle Exacerbates Angiotensin II-Induced Hypertension and Vascular Remodeling Lindsay E. Calderon1, Shu Liu3, Wen Su3, Zhongwen Xie2, Zhenheng Guo3, Wanda Eberhard2, Ming C. Gong2 1 Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, Kentucky, United States of America, 2 Department of Physiology, University of Kentucky, 
Lexington, Kentucky, United States of America, 3 Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, United States of America Abstract Objectives: Calcium independent group VIA phospholipase A2 is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA2b 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 iPLA2b transgenic mice. Method and 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 iPLA2b-Tg than iPLA2b-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 iPLA2b-Tg mice. Analysis revealed no difference in vascular smooth muscle cell proliferation. In contrast, adenovirus-mediated iPLA2b overexpression in cultured vascular smooth muscle cells promoted angiotensin II-induced -leucine incorporation, indicating enhanced hypertrophy. Moreover, angiotensin II infusion-induced c-Jun phosphorylation in vascular smooth muscle cells overexpressing iPLA2b to higher levels, which was abolished by inhibition of 12/15 lipoxygenase. In addition, “ 21526763 we found that angiotensin II up-regulated the endogenous iPLA2b protein in-vitro and in-vivo. Conclusion: The present study reports that iPLA2b up-regulation exacerbates angiotensin II-induced vascular smooth muscle cell hypertrophy, vascular remodeling and hypertension via the 12/15 lipoxygenase and c-Jun pathways. Citation: Calderon LE, Liu S, Su W, Xie Z, Guo Z, et al. iPLA2b Overexpression in Smooth Muscle Exacerbates Angiotensin II-Induced Hypertension and Vascular Remodeling. PLoS ONE 7: e31850. doi:10.1371/journal.pone.0031850 Editor: Gangjian Qin, Northwestern University, United States of America Received October 19, 2011; Accepted January 13, 2012; Published February 20, 2012 Copyright: 2012 Calderon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution UNC0642 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by National Institute of Health grants HL-082791 to M.C.G. and HL-088389 to Z.G. L.E.C. was supported by an American Heart Association Fellowship-09PRE2300152 and a National Institute of Health T32-HL072743. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. E-mail: [email protected] Introduction pletely understood. Evide