Salusin-β Promotes Vascular Smooth Muscle Cell Migration and Intimal Hyperplasia After Vascular Injury<i>via</i>ROS/NFκB/MMP-9 Pathway

Sun, Hai-Jian; Zhao, Mingxia; Ren, Xing-Sheng; Liu, Tongyan; Chen, Qi; Li, Yuehua; Kang, Yu-Ming; Wang, Juejin; Zhu, Guo‐Qing

doi:10.1089/ars.2015.6475

Cited by 95 publications

(82 citation statements)

References 47 publications

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“…VSMCs in culture often mimic the synthetic phenotype, typically expressing MMP-2 in the presence of an autocrine or PDGF loop [37]. Some peptides, such as salusin-β, promote the migration of VSMCs through upregulation of MMP-2 and MMP-9 [18,38]. Here, we found that salusin-α treatment dramatically inhibited MMP-2 and MMP-9 expression in plaques (Fig.…”

Section: Discussionsupporting

confidence: 50%

“…Atherosclerosis development is accelerated by salusin-β via increased acyl-coenzyme A:cholesterol acyltransferase-1 expression in human monocyte-derived macrophages, whereas salusin-α may have the opposite effect: serum salusin-α levels are inversely correlated with the maximum intima-media thickness in patients with coronary artery disease [15,16]. Although there is a link between salusin-α and atherosclerosis [11,16,17], it is unclear whether salusin-α plays a role in the proliferation and migration of SMCs, another important cellular event in atherosclerotic lesion formation, even though some reports have shown that salusin-β promotes SMC migration and proliferation and vascular inflammation and fibrosis [18][19][20]. In this study, we attempted to examine the effects of salusin-α on rabbit atherosclerosis, with emphasis on the role of the peptide in SMCs and the underlying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

Gao

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The proliferation and migration of vascular smooth muscle cells (VSMCs) are key steps in the progression of atherosclerosis. The aim of the present study was to investigate the potential roles of salusin-α in the functions of VSMCs during the development of atherosclerosis. Methods: In vivo, the effects of salusin-α on atherogenesis were examined in rabbits fed a cholesterol diet. The aortas were en face stained with Sudan IV to evaluate the gross atherosclerotic lesion size. The cellular components of atherosclerotic plaques were analyzed by immunohistochemical methods. In vitro, Cell Counting Kit-8 and wound-healing assays were used to assess the effects of salusin-α on VSMC proliferation and migration. In addition, western blotting was used to evaluate the total and phosphorylated levels of Akt (also known as protein kinase B) and mammalian target of rapamycin (mTOR) in VSMCs. Results: Salusin-α infusion significantly reduced the aortic lesion areas of atherosclerosis, with a 39% reduction in the aortic arch, a 71% reduction in the thoracic aorta, and a 71% reduction in the abdominal aorta; plasma lipid levels were unaffected. Immunohistochemical staining showed that salusin-α decreased both macrophage- and VSMC-positively stained areas in atherosclerotic lesions by 54% and 69%, cell proliferative activity in the intima and media of arteriosclerotic lesions, and matrix metalloproteinase 2 (MMP-2) and MMP-9 expression in plaques. Studies using cultured VSMCs showed that salusin-α decreased VSMC migration and proliferation via reduced phosphorylation of Akt and mTOR. Conclusion: Our data indicate that salusin-α suppresses the development of atherosclerosis by inhibiting VSMC proliferation and migration through the Akt/mTOR pathway.

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Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

Gao

Zhang

et al. 2018

Cell Physiol Biochem

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“…As a reactive electrophile, CA could affect Nrf2-independent pathways by directly reacting with other cellular targets. CA may be inhibiting cell proliferation by targeting key pathways such as NF-kB [41], m-TOR [23], or the mitogen-activated protein kinase pathway [42], [43] whose inhibition has been shown to prevent neointimal hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

Cinnamic aldehyde inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia in Zucker Diabetic Fatty rats

2018

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Atherosclerosis remains the number one cause of death and disability worldwide. Atherosclerosis is treated by revascularization procedures to restore blood flow to distal tissue, but these procedures often fail due to restenosis secondary to neointimal hyperplasia. Diabetes mellitus is a metabolic disorder that accelerates both atherosclerosis development and onset of restenosis. Strategies to inhibit restenosis aim at reducing neointimal hyperplasia by inhibiting vascular smooth muscle cell (VSMC) proliferation and migration. Since increased production of reactive oxygen species promotes VSMC proliferation and migration, redox intervention to maintain vascular wall redox homeostasis holds the potential to inhibit arterial restenosis. Cinnamic aldehyde (CA) is an electrophilic Nrf2 activator that has shown therapeutic promise in diabetic rodent models. Nrf2 is a transcription factor that regulates the antioxidant response. Therefore, we hypothesized that CA would activate Nrf2 and would inhibit neointimal hyperplasia after carotid artery balloon injury in the Zucker Diabetic Fatty (ZDF) rat. In primary ZDF VSMC, CA inhibited cell growth by MTT with an EC50 of 118 ± 7 μM. At a therapeutic dose of 100 μM, CA inhibited proliferation of ZDF VSMC in vitro and reduced the proliferative index within the injured artery in vivo, as well as migration of ZDF VSMC in vitro. CA activated the Nrf2 pathway in both ZDF VSMC and injured carotid arteries while also increasing antioxidant defenses and reducing markers of redox dysfunction. Additionally, we noted a significant reduction of neutrophils (69%) and macrophages (78%) within the injured carotid arteries after CA treatment. Lastly, CA inhibited neointimal hyperplasia evidenced by a 53% reduction in the intima:media ratio and a 61% reduction in vessel occlusion compared to arteries treated with vehicle alone. Overall CA was capable of activating Nrf2, and inhibiting neointimal hyperplasia after balloon injury in a rat model of diabetic restenosis.

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“…In previous studies, it has been shown that salusin-β might increase the inflammatory factors by increasing the I-κBa/NF-κB signal pathway activation [21]. Salusin-β weakened the neointima formation stemming from the injury, ROS production, and NOX2 and MMP-9 expression and the p65 translocation of the NF-κB in knock-out rats [42]. In another study, it was reported that salusin-α did not have any effects on IL-1β; however, salusin-β stimulated the expression of IL-1β [43,44].…”

Section: Discussionmentioning

confidence: 93%

“…Our results showed that the caspase-3 expression, which increased in the ethanol-induced ulcer group, decreased after the treatment with salusins. Sun et al [42] conducted a study and reported that salusin-β level increased in relation with the vascular tissue damage. Meanwhile, the protective properties of salusin-α and salusin-β have been reported in myocardial ischemia reperfusion damage [19] and in kidney ischemia reperfusion damage [51].…”

Section: Discussionmentioning

confidence: 99%

Protective effect of salusin-α and salusin-β against ethanol-induced gastric ulcer in rats

Tanyeli

Eraslan

Polat

et al. 2017

Journal of Basic and Clinical Physiology and Pharmacology

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Background: Alcohol consumption has been found to be associated with gastric ulcers, including gastric mucosal lesions. Salusin-α and salusin-β are bioactive peptides having 28 and 20 amino acids, respectively. Salusin-α and salusin-β immunoreactivity has been detected in the stomach and in the intestines. It has been reported that the salusins regulate the cytokine levels and decrease the infarct area in the heart tissue after ischemia. In this study, we investigated the effects of the salusins in the gastric injury formed with ethanol. Methods: Thirty-two sprague Dawley male rats were randomly divided into four groups, including eight rats in each group as follows: Group 1: control; Group 2: ethanol 5 mL/kg; Group 3: ethanol 5 mL/kg + 5 nmol/kg salusin-α; Group 4: ethanol 5 mL/kg + 5 nmol/kg salusin-β. Results: The salusin-α level increased at a significant level in the ulcer group formed with ethanol (p < 0.001); the change in the salusin-β level is not significant. As for malondialdehyde (p < 0.05) and myeloperoxidase (p < 0.001), when compared with the control group, tumor necrosis factor-α (p < 0.05) levels increased in the group to which ethanol was applied and decreased significantly with the application of salusins. Levels of GSH and IL-1β did not change at a significant level. In addition, histopathologic analysis demonstrated that, in salusin-administered groups, mucosal injury and caspase-3 expressions were reduced. Conclusions: The suppression of salusin-α and salusin-β on caspase-3 expression by means of their effects on

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Salusin-β Promotes Vascular Smooth Muscle Cell Migration and Intimal Hyperplasia After Vascular InjuryviaROS/NFκB/MMP-9 Pathway

Cited by 95 publications

References 47 publications

Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

Salusin-α Inhibits Proliferation and Migration of Vascular Smooth Muscle Cell via Akt/mTOR Signaling

Cinnamic aldehyde inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia in Zucker Diabetic Fatty rats

Protective effect of salusin-α and salusin-β against ethanol-induced gastric ulcer in rats

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