Abstract
Migration of vascular smooth muscle cells (VSMCs) is essential for vascular reconstruction in hypertension and several vascular diseases. Our recent study showed that extracellular vesicles derived from vascular adventitial fibroblasts of normal rats inhibited VSMC proliferation by delivering miR155-5p to VSMCs. It is unknown whether miR155-5p inhibits cell migration and oxidative stress in VSMCs of spontaneously hypertensive rats (SHR) and in angiotensin II (Ang II)-treated VSMCs. The purpose of this study was to determine the role of miR155-5p in VSMC migration and its underlying mechanisms. Primary VSMCs were isolated from the aortic media of Wistar-Kyoto rats (WKY) and SHR. Wound healing assay and Boyden chamber assay were used to evaluate VSMC migration. A miR155-5p mimic inhibited, and a miR155-5p inhibitor promoted the migration of VSMC of SHR but had no significant effect on the migration of VSMC of WKY. The miR155-5p mimic inhibited angiotensin-converting enzyme (ACE) mRNA and protein expression in VSMCs. It also reduced superoxide anion production, NAD(P)H oxidase (NOX) activity, as well as NOX2, interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) expression levels in VSMCs of SHR but not in VSMCs of WKY rats. Overexpression of miR155-5p inhibited VSMC migration and superoxide anion and IL-1β production in VSMCs of SHR but had no impact on exogenous Ang II-induced VSMC migration and on superoxide anion and IL-1β production in WKY rats and SHR. These results indicate that miR155-5p inhibits VSMC migration in SHR by suppressing ACE expression and its downstream production of Ang II, superoxide anion, and inflammatory factors. However, miR155-5p had no effects on exogenous Ang II-induced VSMC migration.
Highlights
Vascular smooth muscle cells (VSMCs) are majorly located within the tunica media of vessels.vascular smooth cells (VSMC) migration from arterial media to intima is an essential event in the pathogenesis of several vascular diseases including atherosclerosis, hypertension, restenosis, transplant vasculopathy, and arterial wall injury [1,2]
VSMC migration and on superoxide anion and IL-1β production in WKY rats and spontaneously hypertensive rats (SHR). These results indicate that miR155-5p inhibits VSMC migration in SHR by suppressing angiotensin-converting enzyme (ACE) expression and its downstream production of angiotensin II (Ang II), superoxide anion, and inflammatory factors
MiR155-5p had no effects on exogenous Ang II-induced VSMC migration
Summary
VSMC migration from arterial media to intima is an essential event in the pathogenesis of several vascular diseases including atherosclerosis, hypertension, restenosis, transplant vasculopathy, and arterial wall injury [1,2]. VSMC migration and proliferation are crucial for vascular remodeling. Oxidative stress is originated by an imbalance of reactive oxygen species (ROS) production and antioxidant mechanisms [5,6]. A problem occurs when ROS production exceeds the capacity of antioxidant mechanisms, which further causes cellular damage and inflammation [8]. Oxidative stress greatly contributes to the pathogenesis of many cardiovascular diseases by promoting vascular inflammation and VSMC proliferation, migration, and apoptosis [9,10,11]. Vascular oxidative stress and inflammation are crucial for vascular remodeling in hypertension [12,13,14]
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