scholarly journals Metformin attenuates carotid neointimal hyperplasia by modulating the vascular smooth muscle cell phenotype transformation through upregulation of TET2, Nur77 and calponin

2021 ◽  
Vol 73 (1) ◽  
pp. 135-144
Author(s):  
Hao Lin ◽  
Shuo Cheng ◽  
Zhichao Yuan ◽  
Zhiqiang Yan ◽  
Jifa Zhang
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Neointimal Hyperplasia ◽  
Nuclear Antigen ◽  
Cell Phenotype ◽  
Alpha Smooth Muscle Actin ◽  
And Migration ◽  
Proliferation And Migration

Metformin is a drug used to treat type 2 diabetes based on its effectiveness as well as cardiovascular safety. Metformin has been shown to modulate proliferation and migration of vascular smooth muscle cells (VSMCs), but the underlying mechanisms of the effect of metformin on VSMC function remains unclear. We found that metformin inhibits VSMC proliferation and migration and upregulates the expression of nuclear receptor subfamily 4 group A member 1 (Nur77), ten-eleven translocation 2 (TET2), and calponin in vitro. In the carotid artery balloon injury model of rats, metformin effectively prevented neointimal hyperplasia in the carotid artery, including neointimal thickness, increased neointimal area, and the neointimal area/medial area ratio. It also reduced the number of proliferating cell nuclear antigen (PCNA)+ cells and increased the expression of Nur77, calponin and alpha-smooth muscle actin (?-SMA). These results show that metformin attenuates neointimal hyperplasia in balloon-injured carotid arteries via increased expression of TET2, Nur77 and calponin, and reduced expression of matrix metallopeptidase 9 (MMP-9).

scholarly journals Jujuboside B Inhibits Neointimal Hyperplasia and Prevents Vascular Smooth Muscle Cell Dedifferentiation, Proliferation, and Migration via Activation of AMPK/PPAR-γ Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Zaixiong Ji ◽  
Jiaqi Li ◽  
Jianbo Wang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Neointimal Hyperplasia ◽  
Muscle Cells ◽  
Cell Dedifferentiation ◽  
Ppar Γ ◽  
And Migration ◽  
Proliferation And Migration

The uncontrolled proliferation and migration of vascular smooth muscle cells is a critical step in the pathological process of restenosis caused by vascular intimal hyperplasia. Jujuboside B (JB) is one of the main biologically active ingredients extracted from the seeds of Zizyphus jujuba (SZJ), which has the properties of anti-platelet aggregation and reducing vascular tension. However, its effects on restenosis after vascular intervention caused by VSMCs proliferation and migration remain still unknown. Herein, we present novel data showing that JB treatment could significantly reduce the neointimal hyperplasia of balloon-damaged blood vessels in Sprague-Dawley (SD) rats. In cultured VSMCs, JB pretreatment significantly reduced cell dedifferentiation, proliferation, and migration induced by platelet-derived growth factor-BB (PDGF-BB). JB attenuated autophagy and reactive oxygen species (ROS) production stimulated by PDGF-BB. Besides, JB promoted the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ). Notably, inhibition of AMPK and PPAR-γ partially reversed the ability of JB to resist the proliferation and migration of VSMCs. Taken as a whole, our findings reveal for the first time the anti-restenosis properties of JB in vivo and in vitro after the endovascular intervention. JB antagonizes PDGF-BB-induced phenotypic switch, proliferation, and migration of vascular smooth muscle cells partly through AMPK/PPAR-γ pathway. These results indicate that JB might be a promising clinical candidate drug against in-stent restenosis, which provides a reference for further research on the prevention and treatment of vascular-related diseases.

scholarly journals MicroRNA-145 Involves in the Pathogenesis of Renal Vascular Lesions and May Become a Potential Therapeutic Target in Patients with Juvenile Lupus Nephritis

2019 ◽  
Vol 44 (4) ◽  
pp. 643-655 ◽  
Author(s):  
Zhaomin Cai ◽  
Wei Xiang ◽  
Xiaojie Peng ◽  
Yan Ding ◽  
Wang Liao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Lupus Nephritis ◽  
Smooth Muscle Actin ◽  
Vascular Lesions ◽  
Alpha Smooth Muscle Actin ◽  
Migration Ability ◽  
Phenotypic Transformation ◽  
And Migration ◽  
Renal Vascular ◽  
Proliferation And Migration

Aims: The current study was conducted with the central objective of investigating the expression of microRNA-145 (miR-145) in renal vascular lesions (RVLs) in juvenile lupus nephritis (JLN) and its possible mechanism. Methods: The clinical data of 49 JLN patients confirmed by renal biopsy were collected and followed by grouping according to the RVLs score after hematoxylin-eosin staining: mild, moderate, and severe groups. In situ hybridization was used to detect the expression of miR-145 in renal vessels which was then being compared among different RVLs groups. Up-LV-miR-145 and LV-miR-NC lentiviral vectors were constructed and transfected into human vascular smooth muscle cells (HVSMCs), respectively. After HVSMCs were treated with 10.0 µg/L platelet-derived growth factor (PDGF)-BB for 24 h, the proliferation, migration, and apoptosis of endothelial cells were detected by MTT, Transwell assay, and flow cytometry, respectively. Western blot was used to detect expression of alpha-smooth muscle actin (α-SM-actin) and osteopontin (OPN). Results: The expression of miR-145 in renal vascular cells was statistically significant. The higher the inner membrane ratio, the lesser the miR-145 expression. After treatment with PDGF-BB, expression of miR-145 in HVSMCs decreased, proliferation and migration ability enhanced, apoptosis decreased, α-SM-actin decreased, and OPN increased. The proliferation and migration ability of HVSMCs in the LV-miR-145 group suppressed, apoptosis enhanced, α-SM-actin increased, and OPN decreased. Conclusions: Our study revealed that miR-145 expression decreased with the increase of vascular damage. miR-145 can inhibit proliferation, migration, and differentiation phenotypic transformation of HVSMCs induced by PDGF-BB. miR-145 may be involved in the pathogenesis of RVLs and may be a new target for treatment of RVLs in lupus nephritis.

scholarly journals Mangiferin Inhibits PDGF-BB-Induced Proliferation and Migration of Rat Vascular Smooth Muscle Cells and Alleviates Neointimal Formation in Mice through the AMPK/Drp1 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Qi Wu ◽  
Yuanyang Chen ◽  
Zhiwei Wang ◽  
Xin Cai ◽  
Yanjia Che ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Neointimal Hyperplasia ◽  
Muscle Cells ◽  
Neointimal Formation ◽  
Artery Ligation ◽  
And Migration ◽  
Proliferation And Migration

Mangiferin is a naturally occurring xanthone C-glycoside that is widely found in various plants. Previous studies have reported that mangiferin inhibits tumor cell proliferation and migration. Excessive proliferation and migration of vascular smooth muscle cells (SMCs) is associated with neointimal hyperplasia in coronary arteries. However, the role and mechanism of mangiferin action in neointimal hyperplasia is still unknown. In this study, a mouse carotid artery ligation model was established, and primary rat smooth muscle cells were isolated and used for mechanistic assays. We found that mangiferin alleviated neointimal hyperplasia, inhibited proliferation and migration of SMCs, and promoted platelets derive growth factors-BB- (PDGF-BB-) induced contractile phenotype in SMCs. Moreover, mangiferin attenuated neointimal formation by inhibiting mitochondrial fission through the AMPK/Drp1 signaling pathway. These findings suggest that mangiferin has the potential to maintain vascular homeostasis and inhibit neointimal hyperplasia.

Abstract 22: Histone Deacetylase (HDAC) 4 Controls Neointimal Hyperplasia via Stimulating Proliferation and Migration of Vascular Smooth Muscle Cells

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Tatsuya Usui ◽  
Muneyoshi Okada ◽  
Hideyuki Yamawaki
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Neointimal Hyperplasia ◽  
Muscle Cells ◽  
Cell Counting ◽  
And Migration ◽  
Proliferation And Migration

Histone deacetylases (HDACs) are transcriptional co-regulators. We have recently demonstrated that a class IIa HDAC, HDAC4 promotes reactive oxygen species (ROS)-dependent vascular smooth muscle inflammation and mediates the development of hypertension in spontaneously hypertensive rats. Pathogenesis of hypertension is in part modulated by vascular structural remodeling via proliferation and migration of vascular smooth muscle cells (SMCs). We thus examined whether HDAC4 controls SMCs proliferation and migration. In rat mesenteric arterial SMCs, small interfering RNA (siRNA) against HDAC4 inhibited platelet-derived growth factor (PDGF)-BB-induced SMCs proliferation as determined by a cell counting (51% inhibition, n=7) or bromodeoxyuridine incorporation assay (95% inhibition, n=6) and migration as determined by Boyden chamber assay (71% inhibition, n=3). Expression and activity of HDAC4 were increased by PDGF-BB (30% increase, n=5 and 170% increase, n=4, respectively). HDAC4 siRNA inhibited phosphorylation of p38 (69% inhibition, n=5) and heat shock protein (HSP) 27 (91% inhibition, n=5) and expression of cyclin D1 (58% inhibition, n=5) as measured by Western blotting. HDAC4 siRNA also inhibited PDGF-BB-induce ROS production as measured fluorometrically using 2’ 7’-dichlorofluorescein diacetate (77% inhibition, n=4) and nicotinamide adenine dinucleotide phosphate oxidase activity as measured by lucigenin assay (61% inhibition, n=4). A Ca 2+ /calmodulin (CaM)-dependent protein kinase (CaMK) II inhibitor, KN93 inhibited PDGF-BB-induced SMCs proliferation (58% inhibition, n=4) and migration (75% inhibition, n=3) as well as phosphorylation of HDAC4 (84% inhibition, n=4). In vivo, a class IIa HDACs inhibitor, MC1568 prevented neointimal hyperplasia in mice carotid ligation model (54% inhibition, n=6). MC1568 also inhibited increased activity of HDAC4 in the neointimal lesions. The present results for the first time demonstrate that HDAC4 controls PDGF-BB-induced SMCs proliferation and migration through activation of p38/HSP27 signals via ROS generation in a CaMKII-dependent manner, which may lead to the neointima hyperplasia in vivo.

S-(–)-equol alleviates stenosis of the injured carotid artery in Sprague Dawley rats by preventing the vascular smooth muscle cell phenotypic switch via inhibition of the MAPKp38-NFκBp65 signaling

2020 ◽  
Vol 10 (8) ◽  
pp. 1237-1248
Author(s):  
Hongchen Wu ◽  
Piming Nie ◽  
Zhenghua Zhou ◽  
Jun Hu ◽  
Guangjian Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Vascular Smooth Muscle ◽  
Carotid Stenosis ◽  
Phenotypic Switching ◽  
Sprague Dawley ◽  
Phenotypic Switch ◽  
Sd Rats ◽  
And Migration ◽  
Proliferation And Migration

Phenotypic switching of the vascular smooth muscle cells (VSMCs) is closely related to an in-stent restenosis (ISR). This study aimed to investigate whether S-(–)-equol prevented the phenotypic switch of the VSMCs as a potential treatment of an ISR. The carotid arteries of female Sprague Dawley (SD) rats with or without a carotid injury and ovariectomy were harvested after 4 weeks of treatment with S-(–)-equol. Stenosis of the carotid artery and two phenotype-related proteins-α smooth muscle actin (αSMA) and osteopontin (OPN)-were determined. The proliferation and migration capacities of VSMCs were determined by the CCK-8 and transwell assays, respectively. The expressions of αSMA, OPN, MAPKp38, p-MAPKp38, NF-κBp65, and p-NF-κBp65 were detected by a western blot. S-(–)-equol alleviated carotid stenosis and prevented the VSMC phenotypic switch in female SD rats with a carotid artery injury and a bilateral ovariectomy. S-(–)-equol inhibited the phenotypic switch of VSMCs, which was induced by PDGF-BB, and enhanced the proliferation and migration of VSMCs. The effects of S-(–)-equol on VSMCs were confirmed to be related to the inactivation of the GPER-MAPKp38-NF-κBp65 signaling in vitro and in vivo. Our results indicate that S-(–)-equol affects carotid stenosis by preventing the phenotypic switch of VSMCs via the GPER-MAPKp38-NF-κBp65 signaling pathway.

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