Next Article in Journal
Molecular Mechanisms and Management of a Cutaneous Inflammatory Disorder: Psoriasis
Previous Article in Journal
An Oldie but Goodie: Lithium in the Treatment of Bipolar Disorder through Neuroprotective and Neurotrophic Mechanisms
Previous Article in Special Issue
Subcellular Interactions during Vascular Morphogenesis in 3D Cocultures between Endothelial Cells and Fibroblasts
Article

Differential Effects of sEH Inhibitors on the Proliferation and Migration of Vascular Smooth Muscle Cells

1
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea
2
College of Pharmacy, Chungnam National University, Daejeon 34134, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(12), 2683; https://doi.org/10.3390/ijms18122683
Received: 24 October 2017 / Revised: 30 November 2017 / Accepted: 8 December 2017 / Published: 11 December 2017
(This article belongs to the Special Issue Cell-cell Interactions in Blood Vessels)
Epoxyeicosatrienoic acid (EET) is a cardioprotective metabolite of arachidonic acid. It is known that soluble epoxide hydrolase (sEH) is involved in the metabolic degradation of EET. The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in the pathogenesis of atherosclerosis and restenosis. Thus, the present study investigated the effects of the sEH inhibitor 12-(((tricyclo(3.3.1.13,7)dec-1-ylamino)carbonyl)amino)-dodecanoic acid (AUDA) on platelet-derived growth factor (PDGF)-induced proliferation and migration in rat VSMCs. AUDA significantly inhibited PDGF-induced rat VSMC proliferation, which coincided with Pin1 suppression and heme oxygenase-1 (HO-1) upregulation. However, exogenous 8,9-EET, 11,12-EET, and 14,15-EET treatments did not alter Pin1 or HO-1 levels and had little effect on the proliferation of rat VSMCs. On the other hand, AUDA enhanced the PDGF-stimulated cell migration of rat VSMCs. Furthermore, AUDA-induced activation of cyclooxygenase-2 (COX-2) and subsequent thromboxane A2 (TXA2) production were required for the enhanced migration. Additionally, EETs increased COX-2 expression but inhibited the migration of rat VSMCs. In conclusion, the present study showed that AUDA exerted differential effects on the proliferation and migration of PDGF-stimulated rat VSMCs and that these results may not depend on EET stabilization. View Full-Text
Keywords: soluble epoxide hydrolase; epoxyeicosatrienoic acid; cyclooxygenase-2; vascular smooth muscle cell soluble epoxide hydrolase; epoxyeicosatrienoic acid; cyclooxygenase-2; vascular smooth muscle cell
Show Figures

Graphical abstract

MDPI and ACS Style

Kim, H.S.; Kim, S.K.; Kang, K.W. Differential Effects of sEH Inhibitors on the Proliferation and Migration of Vascular Smooth Muscle Cells. Int. J. Mol. Sci. 2017, 18, 2683. https://doi.org/10.3390/ijms18122683

AMA Style

Kim HS, Kim SK, Kang KW. Differential Effects of sEH Inhibitors on the Proliferation and Migration of Vascular Smooth Muscle Cells. International Journal of Molecular Sciences. 2017; 18(12):2683. https://doi.org/10.3390/ijms18122683

Chicago/Turabian Style

Kim, Hyo S., Sang K. Kim, and Keon W. Kang. 2017. "Differential Effects of sEH Inhibitors on the Proliferation and Migration of Vascular Smooth Muscle Cells" International Journal of Molecular Sciences 18, no. 12: 2683. https://doi.org/10.3390/ijms18122683

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop