Abstract
BackgroundThe migration of vascular smooth muscle cells from the tunica media to the subendothelial region may be a key event in the development of atherosclerosis after arterial injury. In this study, we investigated the potential mechanisms underlying the anti-atherosclerotic effects of Schisandrae Semen essential oil (SSeo) in human aortic smooth muscle cells (HASMCs).MethodsMetalloproteinase-2/9 (MMP-2/9) activity was evaluated by gelatin zymography and gelatinase activity assay kit. The possible mechanisms underlying SSeo-mediated reduction of by tumor necrosis factor (TNF)-α-induced cell invasion and inhibition of secreted and cytosolic MMP-9 production in HASMCs were investigated.ResultsOur results indicate that SSeo treatment has an inhibitory effect on activation as well as expression of MMP-9 induced by TNF-α in HASMCs in a dose-dependent manner without significant cytotoxicity. SSeo attenuated nuclear translocation of TNF-α-mediated nuclear factor-kappa B (NF-κB) and blocked degradation of the NF-κB inhibitor proteins as well as the production of reactive oxygen species. SSeo also reduced TNF-α-induced production of pro-inflammatory mediators such as nitric oxide and prostaglandin E2 and inhibited inducible nitric oxide synthase and cyclooxygenase-2 expression in HASMCs. Furthermore, the Matrigel migration assay showed that SSeo effectively reduced TNF-α-induced HASMC migration compared with that in the control group.ConclusionsTaken together, these results suggest that SSeo treatment suppresses TNF-α-induced HASMC migration by selectively inhibiting MMP-9 expression, which was associated with suppression of the NF-κB signaling pathway. Taken together, these results suggest that SSeo has putative potential anti-atherosclerotic activity.
Highlights
The migration of vascular smooth muscle cells from the tunica media to the subendothelial region may be a key event in the development of atherosclerosis after arterial injury
An increase in matrix metalloproteinases (MMPs)-9 production could contribute to an invasive human aortic smooth muscle cells (HASMCs) phenotype [6,7,8]; we investigated the effect of Semen essential oil (SSeo) on tumor necrosis factor (TNF)-α-induced MMP-9 activation
The levels of tissue inhibitors of metalloproteinase (TIMP)-1 and −2 mRNA and protein showed no significant changes in HASMCs treated with or without TNF-α and SSeo. These results suggest that SSeo suppresses TNF-α-induced MMP-9 activity by inhibiting MMP-9 transcription level in HASMCs, which was not associated with TIMPs expression
Summary
The migration of vascular smooth muscle cells from the tunica media to the subendothelial region may be a key event in the development of atherosclerosis after arterial injury. Proliferation and migration of vascular smooth muscle cells (VSMCs) from the tunica media to the subendothelial region play a major role in the development and progression of atherosclerosis, which is a progressive pathological disorder that often leads to cardiovascular and cerebrovascular diseases. The NF-κB dimer dissociates from IκB and translocates to the nucleus following inflammatory or other stimuli that leads to degradation of the IκB protein. NF-κB binds to promoter regions and induces the expression of a wide variety of genes including various inflammatory factors, adhesion molecules, and MMPs [14,15]
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