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

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.

Chitinase-3 like-protein-1, matrix metalloproteinase -9 and positive intracranial arterial remodelling

“…Persistent high wall flow shear causes the endothelium to produce inflammatory mediators such as nitrogen monoxide and interleukin 6 (IL-6) under long-term chronic pressure (Wang D. et al, 2022), which causes endothelial cell damage and smooth muscle cell apoptosis through a cascade reaction, prompting outward expansion of the vessel wall, resulting in positive remodelling (Myasoedova et al, 2018). Increased macrophage activation, inflammatory cell infiltration, and smooth muscle cell phenotypic changes can occur during the pre-remodelling period (Cai et al, 2021), causing more atherosclerotic plaque formation and eventually leading to outward remodelling of the vessel wall (Di Ieva et al, 2013). Current studies suggest that MMP-9 affects positive arterial remodelling primarily through high wall flow shear, stimulating macrophage activation and causing the release of large amounts of MMPs, which stimulate MMP-9 expression (Frösen et al, 2019).…”

Neurovascular protection of alisol A on cerebral ischemia mice through activating the AKT/GSK3β pathway

“…AKT inhibits inflammation and apoptosis by inactivating GSK3β, and GSK3β promotes translocation of this proapoptotic protein to mitochondria in neurons undergoing apoptosis by directly phosphorylating BAX on Ser163 [ 46 ]. The BAX/Bcl-2 ratio is increased by downregulating the phosphorylation levels of AKT and GSK3β [ 47 ]. Furthermore, activating the AKT/GSK3β pathway has been proven to mediate the survival of hippocampal CA1 neurons after CI [ 48 ].…”

Seleno-Metabolites and Their Precursors: A New Dawn for Several Illnesses?

“…The adaptation of the vascular wall structure to the massive proliferation and reduced apoptosis of the vascular smooth muscle cells (VSMCs) is known as vascular remodeling (VR). It is widely recognized that pathological VR is responsible for numerous cardiovascular conditions, such as atherosclerosis, pulmonary arterial hypertension, and post-angioplasty restenosis [87,88]. Even though stent implantation is an available treatment for the attenuation of the obstruction of the coronary flow related to atherosclerosis pathologies, its detrimental effects have raised the interest in finding new alternatives.…”

“…Although it is necessary to gain further insight into the underlying mechanism of its activity, the data suggest that it might be mediated by the suppression of the AKT and ERK pathways. In view of the former, Na 2 SeO 3 can be considered an attractive potential drug candidate for the treatment of VR-related pathologies [87].…”