Sodium Selenite Attenuates Balloon Injury-Induced and Monocrotaline-Induced Vascular Remodeling in Rats.

Changhong Cai,Ning Zhu,Yijia Xiang,Huan Zhao,Wuming Hu,Lingchun Lv,Lebing Yang,Chunlai Zeng,Yonghui Wu

doi:10.3389/fphar.2021.618493

Changhong Cai, Ning Zhu + Show 7 more

Open Access

https://doi.org/10.3389/fphar.2021.618493

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Abstract

Vascular remodeling (VR), induced by the massive proliferation and reduced apoptosis of vascular smooth muscle cells (VSMCs), is primarily responsible for many cardiovascular conditions, such as restenosis and pulmonary arterial hypertension. Sodium selenite (SSE) is an inorganic selenium, which can block proliferation and stimulate apoptosis of tumor cells; still, its protective effects on VR remains unknown. In this study, we established rat models with carotid artery balloon injury and monocrotaline induced pulmonary arterial hypertension and administered them SSE (0.25, 0.5, or 1 mg/kg/day) orally by feeding tube for 14 consecutive days. We found that SSE treatment greatly ameliorated the development of VR as evidenced by an improvement of its characteristic features, including elevation of the ratio of carotid artery intimal area to medial area, right ventricular hypertrophy, pulmonary arterial wall hypertrophy and right ventricular systolic pressure. Furthermore, PCNA and TUNEL staining of the arteries showed that SSE suppressed proliferation and enhanced apoptosis of VSMCs in both models. Compared with the untreated VR rats, lower expression of PCNA and CyclinD1, but higher levels of Cleaved Caspase-3 and Bax/Bcl-2 were observed in the SSE-treated rats. Moreover, the increased protein expression of MMP2, MMP9, p-AKT, p-ERK, p-GSK3β and β-catenin that occurred in the VR rats were significantly inhibited by SSE. Collectively, treatment with SSE remarkably attenuates the pathogenesis of VR, and this protection may be associated with the inhibition of AKT and ERK signaling and prevention of VSMC’s dysfunction. Our study suggest that SSE is a potential agent for treatment of VR-related diseases.

Highlights

Vascular remodeling (VR) refers to adaptive modifications of the vascular wall structure and plays an essential part in the physiology of vascular homeostasis
The parameters right ventricle systolic pressure (RVSP), right ventricle/left ventricle plus septum weight ratio (RV/LV + S) and right ventricle/body weight ratio (RV/BW) that reflect the severity of pulmonary arterial hypertension, were significantly increased after MCT injection, whereas reduction followed in the Sodium selenite (SSE) 1 mg/kg group (Figures 2A–C)
The results demonstrated that SSE was effective in inhibiting pulmonary arterial hypertension

Summary

Introduction

Vascular remodeling (VR) refers to adaptive modifications of the vascular wall structure and plays an essential part in the physiology of vascular homeostasis. Pathological vascular remodeling is related to the origination and development of numerous cardiovascular conditions such as atherosclerosis, post-angioplasty restenosis and pulmonary arterial hypertension, which have the highest mortality rate in developing as well as developed countries In response to vascular injury, VSMCs turn into a high rate of proliferation and reduce apoptosis, and move to the vessel’s luminal side, which is critical for remodeling processes in vascular disorders (Alexander and Owens, 2012; Bennett et al, 2016; Lacolley et al, 2017). Sodium selenite (SSE) is the most common reagent that is used as a Se supplement for clinical use, which can inhibit tumor cell proliferation and migration as well as induce cell apoptosis (Okuno et al, 2014). SSE manages a spectrum of signals in tumor cells such as AKT, glycogen synthase kinase 3 beta (GSK3β)/β-catenin, extracellular-signal-regulated kinase (ERK), and phosphatase and tensin homologue deleted on chromosome 10 (PTEN), and because of these effects, SSE is a potential novel chemotherapy drug for cancer (Ren et al, 2009; Luo et al, 2013; Gong and Li, 2016; Kim et al, 2020)

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