Abstract
OBJECTIVES: Calcium independent group VIA phospholipase A2 (iPLA2β) is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA2β 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 iPLA2β transgenic (iPLA2β-Tg) 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 iPLA2β-Tg than iPLA2β-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 iPLA2β-Tg mice. Analysis revealed no difference in vascular smooth muscle cell proliferation. In contrast, adenovirus-mediated iPLA2β overexpression in cultured vascular smooth muscle cells promoted angiotensin II-induced [3H]-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 iPLA2β protein in-vitro and in-vivo.
CONCLUSION: The present study reports that iPLA2β up-regulation exacerbates angiotensin II-induced vascular smooth muscle cell hypertrophy, vascular remodeling and hypertension via the 12/15 lipoxygenase and c-Jun pathways.
Document Type
Article
Publication Date
2-20-2012
Digital Object Identifier (DOI)
http://dx.doi.org/10.1371/journal.pone.0031850
Repository Citation
Calderon, Lindsay E; Liu, Shu; Su, Wen; Xie, Zhongwen; Guo, Zhenheng; Eberhard, Wanda; and Gong, Ming C., "iPLA2β Overexpression in Smooth Muscle Exacerbates Angiotensin II-Induced Hypertension and Vascular Remodeling" (2012). Physiology Faculty Publications. 1.
https://uknowledge.uky.edu/physiology_facpub/1
Notes/Citation Information
Published in PLoS One, v. 7, no., 2, p. 31850.
© 2012 Calderon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.