NF2 deficiency accelerates neointima hyperplasia following vascular injury via promoting YAP-TEAD1 interaction in vascular smooth muscle cells

Sun, Xiongshan; Li, Shuang; Gan, Xueqing; Chen, Ken; Yang, Dachun; Yang, Yongjian

doi:10.18632/aging.103240

Cited by 12 publications

(13 citation statements)

References 46 publications

(76 reference statements)

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“…To explore whether PIKfyve affects the proliferation and migration of VSMCs in vivo, we assessed the effect of PIKfyve in an established model of neointima hyperplasia induced by vascular wire injury. 34 To analyze the role of PIKfyve in vascular intima hyperplasia, qPCR and Western blot were used to detect the content of PIKfyve in carotid artery. After 28 days of injury, we observed increased mRNA and protein level of PIKfyve in vessels (Figs.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of PIKfyve Ameliorates the Proliferation and Migration of Vascular Smooth Muscle Cells and Vascular Intima Hyperplasia By Reducing mTORC1 Activity

Wang

Feng

et al. 2022

Journal of Cardiovascular Pharmacology

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This study was designed to investigate the role and mechanism of PIKfyve in the proliferation and migration of vascular smooth muscle cells (VSMCs) and vascular intima hyperplasia. We first observed increased protein levels of PIKfyve, phospho (p)-S6 Ribosomal Protein (S6) Ser235/236 , p-4EBP1 Thr37/46 in VSMCs after 24 hours of platelet-derived growth factor (PDGF)-BB treatment. By using cell counting kit-8 assay, Ki-67 immunofluorescence staining and wound healing assay, we found that PIKfyve inhibition ameliorated the enhanced activity of VSMC proliferation and migration induced by PDGF-BB. Silencing PIKfyve also suppressed the phosphorylation of S6 and 4EBP1 (2 major effectors of mammalian target of rapamycin complex 1), glucose consumption, activity of hexokinase, and LDH in PDGF-BB-challenged VSMCs. After rescuing the phosphorylation of S6 and 4EBP1 by silencing Tsc1, the suppressive effects of PIKfyve inhibition on glucose utilization, proliferation, and migration in VSMCs were abolished. The animal model of vascular restenosis was established in C57BL/6J mice by wire injury. We found the expression of PIKfyve was increased in carotid artery at day 28 after injury. Reducing the activity of PIKfyve alleviated vascular neointima hyperplasia after injury. In conclusion, targeting PIKfyve might be a novel effective method to reduce the proliferation and migration of VSMCs and vascular restenosis by affecting mammalian target of rapamycin complex 1-mediated glucose utilization.

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Section: Resultsmentioning

confidence: 99%

Inhibition of PIKfyve Ameliorates the Proliferation and Migration of Vascular Smooth Muscle Cells and Vascular Intima Hyperplasia By Reducing mTORC1 Activity

Wang

Feng

et al. 2022

Journal of Cardiovascular Pharmacology

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“…To explore the potential role of VRK1 in the proliferation and migration of VSMCs, we firstly examined VRK1 expression in synthetic VSMCs. Platelet-derived growth factor (PDGF)-BB is known to promote phenotypic transition of VSMC ( 10 ). In the current study, VRK1 was upregulated by PDGF-BB stimulation in both dose-dependent manner ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…C57BL/6J mice (Dashuo Animal Science and Technology, Chengdu, Sichuan) were raised as following described: room temperature, 12-hour light/dark cycle, periodic air changes and free access to food and water. Establishing vascular injury model was performed as described before ( 10 ). Briefly, mice were firstly anesthetized and received a small midline incision in the neck area.…”

Section: Methodsmentioning

confidence: 99%

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Inhibition of VRK1 suppresses proliferation and migration of vascular smooth muscle cells and intima hyperplasia after injury via mTORC1/β-catenin axis

Sun¹,

Zhao²,

Wang³

et al. 2022

BMB Rep

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Characterized by abnormal proliferation and migration of vascular smooth muscle cells (VSMCs), neointima hyperplasia is a hallmark of vascular restenosis after percutaneous vascular interventions. Vaccinia-related kinase 1 (VRK1) is a stress adaption-associated ser/thr protein kinase that can induce the proliferation of various types of cells. However, the role of VRK1 in the proliferation and migration of VSMCs and neointima hyperplasia after vascular injury remains unknown. We observed increased expression of VRK1 in VSMCs subjected to platelet-derived growth factor (PDGF)-BB by western blotting. Silencing VRK1 by shVrk1 reduced the number of Ki-67-positive VSMCs and attenuated the migration of VSMCs. Mechanistically, we found that relative expression levels of β-catenin and effectors of mTOR complex 1 (mTORC1) such as phospho (p)-mammalian target of rapamycin (mTOR), p-S6, and p-4EBP1 were decreased after silencing VRK1. Restoration of β-catenin expression by SKL2001 and re-activation of mTORC1 by Tuberous sclerosis 1 siRNA (siTsc1) both abolished shVrk1-mediated inhibitory effect on VSMC proliferation and migration. siTsc1 also rescued the reduced expression of β-catenin caused by VRK1 inhibition. Furthermore, mTORC1 re-activation failed to recover the attenuated proliferation and migration of VSMC resulting from shVrk1 after silencing β-catenin. We also found that the vascular expression of VRK1 was increased after injury. VRK1 inactivation in vivo inhibited vascular injury-induced neointima hyperplasia in a β-catenindependent manner. These results demonstrate that inhibition of VRK1 can suppress the proliferation and migration of VSMC and neointima hyperplasia after vascular injury via mTORC1/β-catenin pathway.

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“…2020ky014; Chengdu, Sichuan, China). Injury model of common carotid artery was established as described in our previous literature [ 18 ]. Briefly, after anaesthetization with pentobarbital (40 mg/kg, intraperitoneal), a small midline incision in the neck area was conducted.…”

Section: Methodsmentioning

confidence: 99%

Plin5 inhibits proliferation and migration of vascular smooth muscle cell through interacting with PGC-1α following vascular injury

Gan¹,

Zhao²,

Chen³

et al. 2022

Bioengineered

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Abnormal proliferation and migration of vascular smooth muscle cell (VSMC) is a hallmark of vascular neointima hyperplasia. Perilipin 5 (Plin5), a regulator of lipid metabolism, is also confirmed to be involved in vascular disorders, such as microvascular endothelial dysfunction and atherosclerosis. To investigate the regulation and function of plin5 in the phenotypic alteration of VSMC, -an animal model of vascular intima hyperplasia was established in C57BL/6 J and Plin5 knockdown (Plin5 ± ) mice by wire injure. Immunohistochemical staining was used to analyze neointima hyperplasia in artery. Ki-67, dihydroethidium immunofluorescence staining and wound healing assay were used to measure proliferation, reactive oxygen species (ROS) generation and migration of VSMC, respectively. Plin5 was downregulated in artery subjected to vascular injury and in VSMC subjected to platelet-derived growth factor (PDGF)-BB. Plin5 knockdown led to accelerated neointima hyperplasia, excessive proliferation and migration of VSMC after injury. In vitro, we observed increased ROS content in VSMC isolated from Plin5 ± mice. Antioxidative N-acetylcysteine (NAC) inhibited VSMC proliferation and migration induced by PDGF-BB or plin5 knockdown. More importantly, plin5-peroxlsome proliferator-activated receptor-γ coactivator (PGC)-1α interaction was also attenuated in VSMC after knockdown of plin5. Overexpression of PGC-1α suppressed PDGF-BB-induced ROS generation, proliferation, and migration in VSMC isolated from Plin5 ± mice. These data suggest that plin5 serves as a potent regulator of VSMC proliferation, migration, and neointima hyperplasia by interacting with PGC-1α and affecting ROS generation.

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NF2 deficiency accelerates neointima hyperplasia following vascular injury via promoting YAP-TEAD1 interaction in vascular smooth muscle cells

Cited by 12 publications

References 46 publications

Inhibition of PIKfyve Ameliorates the Proliferation and Migration of Vascular Smooth Muscle Cells and Vascular Intima Hyperplasia By Reducing mTORC1 Activity

Inhibition of PIKfyve Ameliorates the Proliferation and Migration of Vascular Smooth Muscle Cells and Vascular Intima Hyperplasia By Reducing mTORC1 Activity

Inhibition of VRK1 suppresses proliferation and migration of vascular smooth muscle cells and intima hyperplasia after injury via mTORC1/β-catenin axis

Plin5 inhibits proliferation and migration of vascular smooth muscle cell through interacting with PGC-1α following vascular injury

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