Journal of Shandong University (Health Sciences) ›› 2019, Vol. 57 ›› Issue (12): 37-45.doi: 10.6040/j.issn.1671-7554.0.2019.1022

Previous Articles    

Effects of cylindromatosis on vascular neointima formation and vascular remodeling

YANG Guang1, WANG Xiangdong2, LI Siying2   

  1. 1. Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    2. Department of Physiology &
    Pathophysiology, School of Basic Medical Sciences, Shandong University, Jinan 250012, Shandong, China
  • Published:2022-09-27

PDF (PC)

9

Abstract: Objective To explore the role of cylindromatosis(CYLD)in vascular neointima formation and vascular smooth muscle cells phenotype transformation. Methods Cyld KO(Cyld-/-)mice were used to establish vascular injury models of carotid artery ligation. The neointima formation was observed with H&E and Van Gieson stainings. The cell apoptosis was examined with TUNEL staining, and cell proliferation and inflammation were detected with Ki67, cluster of differentiation 3(CD3)and monocyte chemoattractant protein-1(MCP-1)immunohistiochemistry, respectively. The mRNA expressions of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6)and interleukin-10(IL-10)were determined with qRT-PCR. Vascular smooth muscle cells(VSMCs)of the aortic artery 山 东 大 学 学 报 (医 学 版)57卷12期 -杨光,等. 头帕肿瘤综合征蛋白在血管新生内膜形成及血管重构中的作用 \=-were isolated from Cyld-/- mice. The CYLD expression was examined with immunofluorescence. The growth rate of VSMCs was observed with growth curve and 3H-thymidine intake assay. The effect of THP1 cells adhesion on VSMCs after TNF-ɑ stimulation was tested with monocyte adhesion assay. The expressions of alpha smooth muscle actin(α-SMA)and smooth muscle 22 alpha(SM22α)were measured with Western blotting. Results After carotid artery ligation for 4 weeks, the neointima formation and cell proliferation were more obvious in Cyld-/- mice than in wild type(WT)mice(P<0.01), while there was no significant difference in cell apoptosis. The expressions of CD3, MCP-1, TNF-ɑ, IL-1β and especially IL-6 were significantly higher in Cyld-/- mice than in WT mice(P<0.01), while the expression of IL-10 was significantly lower(P<0.01). CYLD had a low expression rate in cultured VSMCs. The proliferation rate of VSMCs was much higher in Cyld-/- mice than in WT mice. The adhesion effect of THP-1 was more obvious in Cyld-/- mice than in WT mice under TNF-ɑ stimulation(P<0.05). The expressions of α-SMA and SM22α were lower in Cyld-/- mice than in WT mice. Conclusion In vascular injury, CYLD is involved in vascular neointima formation by affecting vascular smooth muscle cells phenotype transformation and therefore plays an essential role in vascular remodeling.

Key words: Cylindromatosis, Vascular smooth muscle cells, Phenotypic transformation, Neointima, Vascular remodeling

CLC Number: 

  • R365
[1] Benjamin Ej, Muntner P, Alonso A, et al. Heart disease and stroke statistics-2019 update: a report from the american heart association [J]. Circulation, 2019, 139(10): 56-528.
[2] Lacolley P, Regnault V, Segers P, et al. Vascular smooth muscle cells and arterial stiffening: relevance in development, aging, and disease [J]. Physiol Rev, 2017, 97(4):1555-1617.
[3] Wang G, Jacquet L, Karamariti E, et al. Origin and differentiation of vascular smooth muscle cells [J]. J Physiol, 2015, 593(14): 3013-3030.
[4] 魏俊成, 贺福初, 王建. 去泛素化酶cyld[J]. 生命科学, 2013, 25(4): 352-357. WEI Juncheng, HE Fuchu, WANG Jian. CYLD: a deubiquitinase [J]. Chinese Bulletin of Life Sciences, 2013, 25(4): 352-357.
[5] Gao J, Sun L, Huo L, et al. Cyld regulates angiogenesis by mediating vascular endothelial cell migration [J]. Blood, 2010, 115(20): 4130-4137.
[6] Bignell Gr, Warren W, Seal S, et al. Identification of the familial cylindromatosis tumour-suppressor gene [J]. Nat Genet, 2000, 25(2): 160-165.
[7] Massoumi R. Ubiquitin chain cleavage: cyld at work[J]. Trends Biochem Sci, 2010, 35(7): 392-399.
[8] Mathis Bj, Lai Y, Qu C, et al. Cyld-mediated signaling and diseases[J]. Curr Drug Targets, 2015, 16(4): 284-294.
[9] Takami Y, Nakagami H, Morishita R, et al. Potential role of cyld(cylindromatosis)as a deubiquitinating enzyme in vascular cells[J]. Am J Pathol, 2008, 172(3): 818-829.
[10] Cui Tg, Ichikawa T, Yang M, et al. An emerging role of deubiquitinating enzyme cylindromatosis(cyld)in the tubulointerstitial inflammation of iga nephropathy[J]. Biochem Biophys Res Commun, 2009, 390(2): 307-312.
[11] Liu S, Lv J, Han L, et al. A pro-inflammatory role of deubiquitinating enzyme cylindromatosis(cyld)in vascular smooth muscle cells[J]. Biochem Biophys Res Commun, 2012, 420(1): 78-83.
[12] Pseftogas A, Gonidas C, Mosialos G. Activation of peroxisome proliferator-activated receptor gamma in mammary epithelial cells upregulates the expression of tumor suppressor cyld to mediate growth inhibition and anti-inflammatory effects [J]. Int J Biochem Cell Biol, 2017, 82: 49-56. doi: 10.1016/j.biocel.2016.11.011.
[13] Klei Lr, Hu D, Panek R, et al. Malt1 protease activation triggers acute disruption of endothelial barrier integrity via cyld cleavage[J]. Cell Rep, 2016, 17(1): 221-232.
[14] 李秀丹, 石立力, 姜晓艳. 血管平滑肌细胞自噬与糖尿病动脉粥样硬化关系的研究进展[J]. 临床心血管病杂志, 2019, 35(1): 92-95. LI Xiudan,SHI Lili,JIANG Xiaoyan.Research progress in relationship between vascular smooth muscle cell autophagy and diabetic atherosclerosi[J]. Journal of Clinical Cardiology, 2019, 35(1): 92-95.
[15] Alexander Mr, Owens Gk. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease [J]. Annu Rev Physiol, 2012, 74: 13-40. doi: 10.1146/annurev-physiol-012110-142315.
[16] Davis-Dusenbery Bn, Wu C, Hata A. Micromanaging vascular smooth muscle cell differentiation and phenotypic modulation[J]. Arterioscler Thromb Vasc Biol, 2011, 31(11): 2370-2377.
[17] Gomez D, Owens Gk. Smooth muscle cell phenotypic switching in atherosclerosis [J]. Cardiovasc Res, 2012, 95(2): 156-164.
[18] Zheng X, Hu X, Zhang W. The phenotype of vascular smooth muscle cells co-cultured with endothelial cells is modulated by pdgfr-beta/iqgap1 signaling in lps-induced intravascular injury [J]. Int J Med Sci, 2019, 16(8): 1149-1156.
[19] Spin Jm, Maegdefessel L, Tsao Ps. Vascular smooth muscle cell phenotypic plasticity: focus on chromatin remodelling [J]. Cardiovasc Res, 2012, 95(2): 147-155.
[20] Shi N, Chen Sy. Smooth muscle cell differentiation: model systems, regulatory mechanisms, and vascular diseases [J]. J Cell Physiol, 2016, 231(4): 777-787.
[21] 毛志敏, 周如丹, 赵学凌, 等. Mcp-1在炎性反应中的研究进展[J]. 医学综述, 2013, 19(6): 964-966.
[22] Song H, Xu J, Lv N, et al. Irisin reverses platelet derived growth factor-bb-induced vascular smooth muscle cells phenotype modulation through stat3 signaling pathway [J]. Biochem Biophys Res Commun, 2016, 479(2): 139-145.
[23] 朱君, 胥虹贝, 周雪灵, 等. 过表达cyld对氧糖剥夺/复氧大鼠原代皮质神经元中nf-κb信号通路的影响[J]. 中国细胞生物学学报, 2019, 41(8): 1551-1557. ZHU Jun, XU Hongbei, ZHOU Xueling, et al. Effect of CYLD Overexpression on NF-κB Signaling Pathway after Oxygen-Glucose Deprivation/Reoxygenation in Rat Primary Cortical Neurons [J]. Chinese Journal of Cell Biology, 2019, 41(8): 1551-1557.
[24] Reiley W, Zhang M, Sun Sc. Negative regulation of jnk signaling by the tumor suppressor cyld [J]. J Biol Chem, 2004, 279(53): 55161-55167.
[25] Wang H, Lai Y, Mathis Bj, et al. Deubiquitinating enzyme cyld mediates pressure overload-induced cardiac maladaptive remodeling and dysfunction via downregulating nrf2 [J]. J Mol Cell Cardiol, 2015, 84: 143-153. doi: 10.1016/j.yjmcc.2015.04.012.
[1] LIU Huimin, LIU Deng, LI Xiaoyu, ZOU Shufeng, JIANG Limin, LI Yuhuan. Effect of Lobelia alkaloids on endothelin-1 signal pathway in a rat model of pulmonary arterial hypertension [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(8): 1-4.
[2] WANG Chun-xiao, XIA Wei, LI Fu-hai, WU Zhi-hua. Effect of fasudil on the expression of BMPR in rats with monocrotalineinduced pulmonary arterial hypertension [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(8): 28-33.
[3] XU Hui1, WANG Yi-guo2, LIU Chang-hong2, LIU Qian2, DU Juan3. Expression of HBV and its effects on the transdifferentiation in HK-2 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(3): 15-20.
[4] XU Zhen-xing1, LIU Rui2， ZHAO Qian1, ZHANG Jun-sheng3, ZHU Shi-ming1. Relationship between matrix metalloproteinases-9 gene polymorphism and the cardiovascular remodeling in  hypertension patients [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2013, 51(2): 61-64.
[5] LI Qun-feng. Effects of the estrogen receptor on stress-induced premature senescence of  vascular smooth muscle cells in vitro [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2011, 49(4): 13-16.
[6] GUO Xue-feng1, ZHANG Ji-dong1, JIANG Hong2, WANG Bo1, REN Min1, FENG Li1 . Effect of Qindan Capsule on expressions of vascular walll collagenⅠand mRNA in spontaneous hypertensive rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(8): 18-21.
[7] LAI Li-ping,ZHANG Ji-dong,LI Li-zhen,LIU Fen-ye. Inhibitory effect of the Yishenhuoxue Capsule on the proliferation of vascular smooth muscle cells induced by HCY in rabbits [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(10): 1011-1015.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd