Please wait a minute...
J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (5): 552-559    DOI: 10.3785/j.issn.1008-9292.2019.10.14
    
Autophagy regulates the function of vascular smooth muscle cells in the formation and rupture of intracranial aneurysms
ZHANG Junhao(),JIN Jinghua,YANG Wei*()
Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou 310058, China
Download: HTML( 8 )   PDF(2080KB)
Export: BibTeX | EndNote (RIS)      

Abstract  

Vascular smooth muscle cells (VSMC) are the main cellular component of vessel wall. The changes of VSMC functions including phenotypic transformation and apoptosis play a critical role in the pathogenesis of intracranial aneurysm (IA). Autophagy can participate in the regulation of vascular function by regulating cell function. In the initial stage of IA, the activation of autophagy can accelerate the phenotypic transformation of VSMC and inhibit VSMC apoptosis. With the progress of IA, the relationship between autophagy and apoptosis changes from antagonism to synergy or promotion, and a large number of apoptotic VSMC lead to the rupture of IA. In this review, we describe the role of autophagy regulating the function of VSMC in the occurrence, development and rupture of IA, for further understanding the pathogenesis of IA and finding molecular targets to prevent the formation and rupture of IA.



Key wordsIntracranial aneurysm/pathology      Muscle, smooth, vascular/cytology      Muscle, smooth, vascular/pathology      Autophagy      Phenotype      Biotransformation      Apoptosis      Review     
Received: 05 May 2019      Published: 04 January 2020
CLC:  R363  
Corresponding Authors: YANG Wei     E-mail: 21718595@zju.edu.cn;yangwei@zju.edu.cn
Cite this article:

ZHANG Junhao,JIN Jinghua,YANG Wei. Autophagy regulates the function of vascular smooth muscle cells in the formation and rupture of intracranial aneurysms. J Zhejiang Univ (Med Sci), 2019, 48(5): 552-559.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2019.10.14     OR     http://www.zjujournals.com/med/Y2019/V48/I5/552


自噬调控血管平滑肌细胞功能在颅内动脉瘤形成和破裂中的作用

血管平滑肌细胞作为血管壁的主要细胞成分,其功能(表型转化、凋亡等)调节在颅内动脉瘤发病中发挥了重要作用。自噬可通过参与细胞功能调控进而参与血管功能的调节。在颅内动脉瘤起始阶段,自噬的激活促使血管平滑肌细胞发生表型转化,并抑制其凋亡;随着颅内动脉瘤的发展,自噬的激活与细胞凋亡由最先的对抗关系转化为协同或推动关系,血管平滑肌细胞大量凋亡导致颅内动脉瘤破裂。本文对自噬调控血管平滑肌细胞功能在颅内动脉瘤发生、发展以及破裂过程中的作用进行了系统阐述,以期为深入理解颅内动脉瘤的发病机制及寻找阻止颅内动脉瘤形成和破裂的分子靶点提供理论基础。


关键词: 颅内动脉瘤/病理学,  血管平滑肌/细胞:血管平滑肌/病理学:自噬,  表型,  生物转化,  细胞凋亡,  综述 
Fig 1 Autophagy-related signaling pathways regulate the functions of VSMC
[1]   LI X G , WANG Y B . SRPK1 gene silencing promotes vascular smooth muscle cell proliferation and vascular remodeling via inhibition of the PI3K/Akt signaling pathway in a rat model of intracranial aneurysms[J]. CNS Neurosci Ther, 2019, 25 (2): 233- 244
doi: 10.1111/cns.13043
[2]   PETRIDIS A K , KAMP M A , CORNELIUS J F et al. Aneurysmal subarachnoid hemorrhage[J]. Dtsch Arztebl Int, 2017, 114 (13): 226- 236
[3]   KAMIO Y , MIYAMOTO T , KIMURA T et al. Roles of nicotine in the development of intracranial aneurysm rupture[J]. Stroke, 2018, 49 (10): 2445- 2452
doi: 10.1161/STROKEAHA.118.021706
[4]   LIU P , SONG Y , ZHOU Y et al. Cyclic mechanical stretch induced smooth muscle cell changes in cerebral aneurysm progress by reducing collagen type iv and collagen type vi levels[J]. Cell Physiol Biochem, 2018, 45 (3): 1051- 1060
[5]   STARKE R M , CHALOUHI N , DING D et al. Vascular smooth muscle cells in cerebral aneurysm pathogenesis[J]. Transl Stroke Res, 2014, 5 (3): 338- 346
doi: 10.1007/s12975-013-0290-1
[6]   SUN L , ZHAO M , LIU A et al. Shear stress induces phenotypic modulation of vascular smooth muscle cells via ampk/mtor/ulk1-mediated autophagy[J]. Cell Mol Neurobiol, 2018, 38 (2): 541- 548
[7]   SUN L , ZHAO M , ZHANG J et al. MiR-29b downregulation induces phenotypic modulation of vascular smooth muscle cells: implication for intracranial aneurysm formation and progression to rupture[J]. Cell Physiol Biochem, 2017, 41 (2): 510- 518
[8]   PAWLOWSKA E , SZCZEPANSKA J , WISNIEWSKI K et al. NF-kappaB-mediated inflammation in the pathogenesis of intracranial aneurysm and subarachnoid hemorrhage. Does autophagy play a role?[J]. Int J Mol Sci, 2018, 19 (4):
[9]   WANG L , ZHANG J , FU W et al. Association of smooth muscle cell phenotypes with extracellular matrix disorders in thoracic aortic dissection[J]. J Vasc Surg, 2012, 56 (6): 1698- 1709, 1709.e1
doi: 10.1016/j.jvs.2012.05.084
[10]   ALEXANDER M R , OWENS G K . 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
[11]   CHALOUHI N , ALI M S , JABBOUR P M et al. Biology of intracranial aneurysms: role of inflammation[J]. J Cereb Blood Flow Metab, 2012, 32 (9): 1659- 1676
doi: 10.1038/jcbfm.2012.84
[12]   SIBON I , MERCIER N , DARRET D et al. Association between semicarbazide-sensitive amine oxidase, a regulator of the glucose transporter, and elastic lamellae thinning during experimental cerebral aneurysm development: laboratory investigation[J]. J Neurosurg, 2008, 108 (3): 558- 566
doi: 10.3171/JNS/2008/108/3/0558
[13]   KOSIERKIEWICZ T A , FACTOR S M , DICKSON D W . Immunocytochemical studies of atherosclerotic lesions of cerebral berry aneurysms[J]. J Neuropathol Exp Neurol, 1994, 53 (4): 399- 406
doi: 10.1097/00005072-199407000-00012
[14]   FR?SEN J , PIIPPO A , PAETAU A et al. Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases[J]. Stroke, 2004, 35 (10): 2287- 2293
doi: 10.1161/01.STR.0000140636.30204.da
[15]   FR?SEN J , MARJAMAA J , MYLL?RNIEMI M et al. Contribution of mural and bone marrow-derived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model[J]. Neurosurgery, 2006, 58 (5): 936- 944
doi: 10.1227/01.NEU.0000210260.55124.A4
[16]   KILIC T , SOHRABIFAR M , KURTKAYA O et al. Expression of structural proteins and angiogenic factors in normal arterial and unruptured and ruptured aneurysm walls[J]. Neurosurgery, 2005, 57 (5): 997- 1007
doi: 10.1227/01.NEU.0000180812.77621.6C
[17]   NAKAJIMA N , NAGAHIRO S , SANO T et al. Phenotypic modulation of smooth muscle cells in human cerebral aneurysmal walls[J]. Acta Neuropathol, 2000, 100 (5): 475- 480
doi: 10.1007/s004010000220
[18]   GUO F , LI Z , SONG L et al. Increased apoptosis and cysteinyl aspartate specific protease-3 gene expression in human intracranial aneurysm[J]. J Clin Neurosci, 2007, 14 (6): 550- 555
doi: 10.1016/j.jocn.2005.11.018
[19]   GARCIA-HUERTA P , TRONCOSO-ESCUDERO P , JEREZ C et al. The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases?[J]. Brain Res, 2016, 1649 (Pt B): 173- 180
[20]   RYTER S W , MIZUMURA K , CHOI A M . The impact of autophagy on cell death modalities[J]. Int J Cell Biol, 2014, 2014 502676
[21]   GUMP J M , THORBURN A . Autophagy and apoptosis: what is the connection?[J]. Trends Cell Biol, 2011, 21 (7): 387- 392
doi: 10.1016/j.tcb.2011.03.007
[22]   MARINO G , NISO-SANTANO M , BAEHRECKE E H et al. Self-consumption: the interplay of autophagy and apoptosis[J]. Nat Rev Mol Cell Biol, 2014, 15 (2): 81- 94
[23]   MIZUSHIMA N , KOMATSU M . Autophagy: renovation of cells and tissues[J]. Cell, 2011, 147 (4): 728- 741
doi: 10.1016/j.cell.2011.10.026
[24]   LAAKSAMO E , RAMACHANDRAN M , FROSEN J et al. Intracellular signaling pathways and size, shape, and rupture history of human intracranial aneurysms[J]. Neurosurgery, 2012, 70 (6): 1565- 1573
doi: 10.1227/NEU.0b013e31824c057e
[25]   WANG C , QU B , WANG Z et al. Proteomic identification of differentially expressed proteins in vascular wall of patients with ruptured intracranial aneurysms[J]. Atherosclerosis, 2015, 238 (2): 201- 206
doi: 10.1016/j.atherosclerosis.2014.11.027
[26]   SALABEI J K , CUMMINS T D , SINGH M et al. PDGF-mediated autophagy regulates vascular smooth muscle cell phenotype and resistance to oxidative stress[J]. Biochem J, 2013, 451 (3): 375- 388
doi: 10.1042/BJ20121344
[27]   WEN J , WANG J , GUO L et al. Chemerin stimulates aortic smooth muscle cell proliferation and migration via activation of autophagy in VSMCs of metabolic hypertension rats[J]. Am J Transl Res, 2019, 11 (3): 1327- 1342
[28]   LI H , LI J , LI Y et al. Sonic hedgehog promotes autophagy of vascular smooth muscle cells[J]. Am J Physiol Heart Circ Physiol, 2012, 303 (11): H1319- H1331
doi: 10.1152/ajpheart.00160.2012
[29]   YAO Y , LI H , DA X et al. SUMOylation of Vps34 by SUMO1 promotes phenotypic switching of vascular smooth muscle cells by activating autophagy in pulmonary arterial hypertension[J]. Pulm Pharmacol Ther, 2019, 55 38- 49
doi: 10.1016/j.pupt.2019.01.007
[30]   DE NIGRIS F , RIENZO M , SESSA M et al. Glycoxydation promotes vascular damage via MAPK-ERK/JNK pathways[J]. J Cell Physiol, 2012, 227 (11): 3639- 3647
doi: 10.1002/jcp.24070
[31]   GWINN D M , SHACKELFORD D B , EGAN D F et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint[J]. Mol Cell, 2008, 30 (2): 214- 226
doi: 10.1016/j.molcel.2008.03.003
[32]   KIM J , KUNDU M , VIOLLET B et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1[J]. Nat Cell Biol, 2011, 13 (2): 132- 141
doi: 10.1038/ncb2152
[33]   BERGE J , BLANCO P , ROORYCK C et al. Understanding flow patterns and inflammatory status in intracranial aneurysms: Towards a personalized medicine[J]. J Neuroradiol, 2016, 43 (2): 141- 147
[34]   SONG L , HUANG Y , HOU X et al. PINK1/parkin-mediated mitophagy promotes resistance to sonodynamic therapy[J]. Cell Physiol Biochem, 2018, 49 (5): 1825- 1839
doi: 10.1159/000493629
[35]   HE L , ZHOU Q , HUANG Z et al. PINK1/Parkin-mediated mitophagy promotes apelin-13-induced vascular smooth muscle cell proliferation by AMPKalpha and exacerbates atherosclerotic lesions[J]. J Cell Physiol, 2019, 234 (6): 8668- 8682
doi: 10.1002/jcp.27527
[36]   MARTIN K A , RZUCIDLO E M , MERENICK B L et al. The mTOR/p70 S6K1 pathway regulates vascular smooth muscle cell differentiation[J]. Am J Physiol Cell Physiol, 2004, 286 (3): C507- C517
doi: 10.1152/ajpcell.00201.2003
[37]   HOSAKA K , HOH B L . Inflammation and cerebral aneurysms[J]. Transl Stroke Res, 2014, 5 (2): 190- 198
doi: 10.1007/s12975-013-0313-y
[38]   CEBRAL J , OLLIKAINEN E , CHUNG B J et al. Flow conditions in the intracranial aneurysm lumen are associated with inflammation and degenerative changes of the aneurysm wall[J]. AJNR Am J Neuroradiol, 2017, 38 (1): 119- 126
doi: 10.3174/ajnr.A4951
[39]   CHALOUHI N , HOH B L , HASAN D . Review of cerebral aneurysm formation, growth, and rupture[J]. Stroke, 2013, 44 (12): 3613- 3622
doi: 10.1161/STROKEAHA.113.002390
[40]   GARCIA-MIGUEL M, RIQUELME J A, NORAMBUENA-SOTO I, et al. Autophagy mediates tumor necrosis factor-alpha-induced phenotype switching in vascular smooth muscle A7r5 cell line[J/OL]. PLoS One, 2018, 13(5): e0197210.
[41]   AN Z , QIAO F , LU Q et al. Interleukin-6 downregulated vascular smooth muscle cell contractile proteins via ATG4B-mediated autophagy in thoracic aortic dissection[J]. Heart Vessels, 2017, 32 (12): 1523- 1535
doi: 10.1007/s00380-017-1054-8
[42]   CHENG C I , LEE Y H , CHEN P H et al. Free fatty acids induce autophagy and lox-1 upregulation in cultured aortic vascular smooth muscle cells[J]. J Cell Biochem, 2017, 118 (5): 1249- 1261
doi: 10.1002/jcb.25784
[43]   WU Y , LIU G , CHEN W et al. 5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside reduces intimal hyperplasia of tissue engineering blood vessel by inhibiting phenotype switch of vascular smooth muscle cell[J]. J Biomed Mater Res B Appl Biomater, 2017, 105 (4): 744- 752
doi: 10.1002/jbm.b.33585
[44]   WU H , SONG A , HU W et al. The anti-atherosclerotic effect of paeonol against vascular smooth muscle cell proliferation by up-regulation of autophagy via the AMPK/mTOR signaling pathway[J]. Front Pharmacol, 2017, 8 948
[45]   SHINTANI T , KLIONSKY D J . Autophagy in health and disease: a double-edged sword[J]. Science, 2004, 306 (5698): 990- 995
doi: 10.1126/science.1099993
[46]   AN X R , LI X , WEI W et al. Prostaglandin e1 inhibited diabetes-induced phenotypic switching of vascular smooth muscle cells through activating autophagy[J]. Cell Physiol Biochem, 2018, 50 (2): 745- 756
[47]   ZHENG Y H , TIAN C , MENG Y et al. Osteopontin stimulates autophagy via integrin/CD44 and p38 MAPK signaling pathways in vascular smooth muscle cells[J]. J Cell Physiol, 2012, 227 (1): 127- 135
doi: 10.1002/jcp.22709
[48]   MALLICK D J , KOROTKOV A , LI H et al. Nuphar alkaloids induce very rapid apoptosis through a novel caspase-dependent but BAX/BAK-independent pathway[J]. Cell Biol Toxicol, 2019,
[49]   MENG Y , LIN Z M , GE N et al. Ursolic acid induces apoptosis of prostate cancer cells via the PI3K/Akt/mTOR pathway[J]. Am J Chin Med, 2015, 43 (7): 1471- 1486
doi: 10.1142/S0192415X15500834
[50]   QIU C , ZHENG H , TAO H et al. Vitamin K2 inhibits rat vascular smooth muscle cell calcification by restoring the Gas6/Axl/Akt anti-apoptotic pathway[J]. Mol Cell Biochem, 2017, 433 (1-2): 149- 159
doi: 10.1007/s11010-017-3023-z
[51]   ROTLLAN N , WANSCHEL A C , FERNANDEZ-HERNANDO A et al. Genetic evidence supports a major role for akt1 in vsmcs during atherogenesis[J]. Circ Res, 2015, 116 (11): 1744- 1752
doi: 10.1161/CIRCRESAHA.116.305895
[52]   ALLARD D , FIGG N , BENNETT M R et al. Akt regulates the survival of vascular smooth muscle cells via inhibition of FoxO3a and GSK3[J]. J Biol Chem, 2008, 283 (28): 19739- 19747
doi: 10.1074/jbc.M710098200
[53]   P T , H W , J Z et al. Rapamycin-induced miR-30a downregulation inhibits senescence of VSMCs by targeting Beclin1[J]. Int J Mol Med, 2019, 43 (3): 1311- 1320
[54]   GROSS A , KATZ S G . Non-apoptotic functions of BCL-2 family proteins[J]. Cell Death Differ, 2017, 24 (8): 1348- 1358
doi: 10.1038/cdd.2017.22
[55]   MAIURI M C , LE TOUMELIN G , CRIOLLO A et al. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1[J]. EMBO J, 2007, 26 (10): 2527- 2539
doi: 10.1038/sj.emboj.7601689
[56]   TULAMO R , FROSEN J , JUNNIKKALA S et al. Complement system becomes activated by the classical pathway in intracranial aneurysm walls[J]. Lab Invest, 2010, 90 (2): 168- 179
doi: 10.1038/labinvest.2009.133
[57]   DING Z , WANG X , SCHNACKENBERG L et al. Regulation of autophagy and apoptosis in response to ox-LDL in vascular smooth muscle cells, and the modulatory effects of the microRNA hsa-let-7 g[J]. Int J Cardiol, 2013, 168 (2): 1378- 1385
doi: 10.1016/j.ijcard.2012.12.045
[58]   TANG B , DONG X , WEI Z et al. Enhanced autophagy by everolimus contributes to the antirestenotic mechanisms in vascular smooth muscle cells[J]. J Vasc Res, 2014, 51 (4): 259- 268
doi: 10.1159/000365927
[59]   LA COLLA A , VASCONSUELO A , MILANESI L et al. 17beta-estradiol protects skeletal myoblasts from apoptosis through p53, Bcl-2, and FoxO families[J]. J Cell Biochem, 2017, 118 (1): 104- 115
doi: 10.1002/jcb.25616
[60]   LI D Y , BUSCH A , JIN H et al. H19 induces abdominal aortic aneurysm development and progression[J]. Circulation, 2018, 138 (15): 1551- 1568
doi: 10.1161/CIRCULATIONAHA.117.032184
[1] CHEN Dianyu,QI Ming. Research progress on uniparental disomy in cancer[J]. J Zhejiang Univ (Med Sci), 2019, 48(5): 560-566.
[2] LIN Jing,CHEN Zhimin. Research progress on early identification of severe adenovirus pneumonia in children[J]. J Zhejiang Univ (Med Sci), 2019, 48(5): 567-572.
[3] XU Jiajun,SHU Qiang. Application of 3D printing techniques in treatment of congenital heart disease[J]. J Zhejiang Univ (Med Sci), 2019, 48(5): 573-579.
[4] HUANG Shumin,ZHAO Zhengyan. Advances in newborn screening and immune system reconstitution of severe combined immunodeficiency[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 351-357.
[5] YE Qing,ZHANG Yingying,WANG Jingjing,MAO Jianhua. Analysis of Alport syndrome induced by type IV collagen alpha 5 gene mutation in two families[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 384-389.
[6] TONG Fan,YANG Rulai,LIU Chang,WU Dingwen,ZHANG Ting,HUANG Xinwen,HONG Fang,QIAN Guling,HUANG Xiaolei,ZHOU Xuelian,SHU Qiang,ZHAO Zhengyan. Screening for hereditary tyrosinemia and genotype analysis in newborns[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 459-464.
[7] CHEN Guangjie,WANG Xiaohao,TANG Daxing. Progress on evaluation, diagnosis and management of disorders of sex development[J]. J Zhejiang Univ (Med Sci), 2019, 48(4): 358-366.
[8] ZHANG Jianmin. Advances in surgical treatment of ischemic cerebrovascular disease[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 233-240.
[9] WU Yuxing, ZHANG Shihong, CHEN Zhong. The roles of habenula and related neural circuits in neuropsychiatric diseases[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 310-317.
[10] ZHANG Yunzhu, ZHU Chunpeng, LU Xinliang. Advances in serum biomarkers for early diagnosis of gastric cancer[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 326-333.
[11] MA Jing, HE Wenlong, GAO Chongyang, YU Ruiyun, XUE Peng, NIU Yongchao. Glucosides of chaenomeles speciosa attenuate ischemia/reperfusion-induced brain injury by regulating NF-κB P65/TNF-α in mouse model[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 289-295.
[12] ZHU Ziling, TAN Jing, DENG Hong. Nucleus translocation of membrane/cytoplasm proteins in tumor cells[J]. J Zhejiang Univ (Med Sci), 2019, 48(3): 318-325.
[13] Baboo Kalianee Devi,CHEN Zhengyun,ZHANG Xinmei. Progress on medical treatment in the management of adenomyosis[J]. J Zhejiang Univ (Med Sci), 2019, 48(2): 142-147.
[14] WU Binbin,YANG Yi. Biomarkers of cardiac surgery-associated acute kidney injury: a narrative review[J]. J Zhejiang Univ (Med Sci), 2019, 48(2): 224-229.
[15] WANG Yaqi,JIN Jinghua. Roles of macrophages in formation and progression of intracranial aneurysms[J]. J Zhejiang Univ (Med Sci), 2019, 48(2): 204-213.