Salusin-β Promotes Vascular Smooth Muscle Cell Migration and Intimal Hyperplasia After Vascular InjuryviaROS/NFκB/MMP-9 Pathway
- 20 June 2016
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antioxidants and Redox Signaling
- Vol. 24 (18), 1045-1057
- https://doi.org/10.1089/ars.2015.6475
Abstract
Aims: Media-to-intima migration of vascular smooth muscle cells (VSMCs) is critical to intimal thickening in atherosclerosis and restenosis after coronary angioplasty. The aim of this study is to determine the effects of salusin-β on VSMC migration and intimal hyperplasia after vascular injury and the underlying mechanism. Results:In vitro, salusin-β promoted VSMC migration, which was attenuated by matrix metalloproteinase (MMP)-9 inhibition. Inhibition or knockdown of p65-nuclear factor kappa beta (NFκB) in VSMCs suppressed salusin-β-induced MMP-9 expression and VSMC migration. Salusin-β increased NADPH oxidase 2 (NOX2) expression and reactive oxygen species (ROS) production, which were prevented by NOX2-small interfering RNA (siRNA) transfection. Salusin-β-induced p65-NFκB translocation, MMP-9 expression, and VSMC migration were inhibited by ROS scavenger, NADPH oxidase inhibitor, or NOX2-siRNA. In vivo, carotid artery ligation-induced vascular injury resulted in intimal hyperplasia in injured artery in rats. Salusin-β was upregulated in the injured carotid arteries of rats, which was attributed to reduced miR-133a-3p expression. Knockdown of salusin-β with siRNA attenuated the vascular injury-induced intimal thickening, p65-NFκB nuclear translocation, and NOX2 and MMP-9 expressions in rats. Innovation: Salusin-β is a critical modulator in VSMC migration and neointima formation in response to vascular injury. Conclusions: Salusin-β promotes VSMC migration and vascular injury-induced intimal hyperplasia via MMP-9 accumulation due to NOX2 activation, followed by ROS production, IκBα phosphorylation and degradation, and p65-NFκB translocation. We propose that salusin-β may be important in the VSMC migration and neointima of some vascular diseases. Antioxid. Redox Signal. 24, 1045–1057.Keywords
This publication has 47 references indexed in Scilit:
- Simvastatin induces NFκB/p65 down-regulation and JNK1/c-Jun/ATF-2 activation, leading to matrix metalloproteinase-9 (MMP-9) but not MMP-2 down-regulation in human leukemia cellsBiochemical Pharmacology, 2014
- Mechanotransduction: Forces, Sensors, and Redox SignalingAntioxidants and Redox Signaling, 2014
- Postprandial lipoproteins and the molecular regulation of vascular homeostasisProgress in Lipid Research, 2013
- Salusin-alpha and -beta expression in heart and aorta with and without metabolic syndromeBiotechnic & Histochemistry, 2013
- Long-term zinc deprivation accelerates rat vascular smooth muscle cell proliferation involving the down-regulation of JNK1/2 expression in MAPK signalingAtherosclerosis, 2013
- Salusin-? in paraventricular nucleus increases blood pressure and sympathetic outflow via vasopressin in hypertensive rats.Cardiovascular Research, 2013
- A Chinese herbal formula "Gan-Lu-Yin" suppresses vascular smooth muscle cell migration by inhibiting matrix metalloproteinase-2/9 through the PI3K/AKT and ERK signaling pathwaysBMC Complementary and Alternative Medicine, 2012
- Does Uremia Cause Vascular DysfunctionKidney and Blood Pressure Research, 2011
- Regulation of smooth muscle cells in development and vascular disease: current therapeutic strategiesExpert Review of Cardiovascular Therapy, 2006
- Allograft-Induced Proliferation of Vascular Smooth Muscle Cells: Potential Targets for Treating Transplant VasculopathyCurrent Vascular Pharmacology, 2003