脉管异常的ISSVA分类概要及分子生物学研究进展

doi:10.19438/j.cjoms.2023.03.014

中国口腔颌面外科杂志 ›› 2023, Vol. 21 ›› Issue (3): 286-290.doi: 10.19438/j.cjoms.2023.03.014

脉管异常的ISSVA分类概要及分子生物学研究进展

李晓¹, 范新东^2,*, 郑家伟^3,*

1.上海交通大学医学院附属第九人民医院口腔第二门诊部,2.介入科,3.口腔颌面-头颈肿瘤科,上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,上海 200011

收稿日期:2022-11-10 修回日期:2022-12-02 出版日期:2023-05-20 发布日期:2023-08-16
通讯作者: 范新东,E-mail: fanxindong@aliyun.com;郑家伟,E-mail: davidzhnegjw@hotmail.com。^*共同通信作者
作者简介:李晓（1991-）,女,博士,E-mail: 1315771252@qq.com

Summary of ISSVA classification of vascular anomalies and review of literature in molecular biology

LI Xiao¹, FAN Xin-dong², ZHENG Jia-wei³

1. Second Dental Center, 2. Department of Interventional Therapy, 3. Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology. Shanghai 200011, China

Received:2022-11-10 Revised:2022-12-02 Online:2023-05-20 Published:2023-08-16

摘要/Abstract

摘要： 脉管异常类疾病是一组疾病的总称,国际脉管异常研究学会（ISSVA）将其分为2大类：脉管肿瘤和脉管畸形。本文结合脉管异常类疾病的分子病理学表现,对其遗传学改变的最新研究成果加以总结。在球形静脉畸形中,突变的球蛋白可能通过与c-met的相互作用激活PI3K信号。此外,它们可能抑制TGF-β介导的平滑肌细胞分化,并诱导所谓的血管球细胞增殖。淋巴管畸形中的PIK3CA突变可能刺激VEGF-C或VEGFR3表达,诱导PIK3CA与细胞膜结合;或通过激活下游Akt/mTOR,促进细胞增殖、趋化性和血管生成。动静脉畸形中的RAS通路突变可能激活MEK/ERK信号,RAS激活可能诱导内皮细胞形态变化、出芽行为增加、血管管腔扩大以及动脉和静脉之间异常连接而不伴有细胞增殖。婴幼儿血管瘤中VEGFR2和TEM8突变导致VEGFR2、TEM8和整合素之间的相互作用增加,由此导致整合素/NFATc2/VEGFR1通路失活,导致VEGFR2磷酸化和内皮活化。

关键词: 静脉畸形, 淋巴管畸形, 婴幼儿血管瘤, 分子生物学

Abstract: Vascular abnormalities are the general name of a group of diseases, which are divided into two categories by the International Society for the Study of Vascular Anomalies(ISSVA): vascular tumors and vascular malformations. In this paper, the latest research results of genetic changes in vascular diseases were summarized in combination with their molecular pathological manifestations. In glomuvenous malformations, the mutant globulin may activate PI3K signal through interaction with c-met. In addition, they may inhibit TGF-β-mediating smooth muscle cell differentiation and induce proliferation of so-called vascular globular cells. The mutation of PIK3CA in lymphatic malformation may stimulate the expression of VEGF-C or VEGFR3, induce the combination of PIK3CA with cell membrane, or increase cell proliferation, chemotaxis and angiogenesis by activating downstream Akt/mTOR. Mutation of RAS pathway in AVM may activate MEK/ERK signal, and RAS activation may induce morphological changes of endothelial cells, increase of budding behavior, expansion of vascular lumen, and abnormal connection between arteries and veins without cell proliferation. Mutation of VEGFR2 and TEM8 in infantile hemangioma leads to increased interaction between VEGFR2, TEM8 and integrin, and the resulting inactivation of integrin/NFATc2/VEGFR1 pathway may lead to phosphorylation of VEGFR2 and endothelial activation.

Key words: Venous malformation, Lymphatic malformation, Infantile hemangioma, Molecular biology

中图分类号:

R739.8

李晓, 范新东, 郑家伟. 脉管异常的ISSVA分类概要及分子生物学研究进展[J]. 中国口腔颌面外科杂志, 2023, 21(3): 286-290.

LI Xiao, FAN Xin-dong, ZHENG Jia-wei. Summary of ISSVA classification of vascular anomalies and review of literature in molecular biology[J]. China J Oral Maxillofac Surg, 2023, 21(3): 286-290.

参考文献

[1] 郑家伟, 赵泽亮. 婴幼儿血管瘤与脉管畸形的循证治疗研究进展[J]. 口腔疾病防治, 2021, 29(11): 721-732.
Zheng JW, Zhao ZL.Progress in evidencebased research on the clinical treatment of infantile hemangioma and vascular malformations[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2021, 29(11): 721-732.
[2] Kunimoto K, Yamamoto Y, Jinnin M.ISSVA classification of vascular anomalies and molecular biology[J]. Int J Mol Sci, 2022, 23(4): 2358-2371.
[3] Castillo SD, Tzouanacou E, Zaw-Thin M, et al. Somatic activating mutations in PIK3CA cause sporadic venous malformations in mice and humans[J]. Sci Transl Med, 2016, 8(332): 332ra43.
[4] Castel P, Carmona FJ, Grego-Bessa J, et al. Somatic PIK3CA mutations as a driver of sporadic venous malformations[J]. Sci Transl Med, 2016, 8(332): 332ra42.
[5] di Blasio L, Puliafito A, Gagliardi PA, et al. PI3K/mTOR inhibition promotes the regression of experimental vascular malformations driven by PIK3CA-activating mutations[J]. Cell Death Dis, 2018,9(2):45-60.
[6] Fereydooni A, Dardik A, Nassiri N.Molecular changes associated with vascular malformations[J]. J Vasc Surg, 2019, 70(1):314-326.
[7] Castillo SD, Baselga E, Graupera M.PIK3CA mutations in vascular malformations[J]. Curr Opin Hematol, 2019, 26(3):170-178.
[8] Blesinger H, Kaulfuβ S, Aung T, et al.PIK3CA mutations are specifically localized to lymphatic endothelial cells of lymphatic malformations[J]. PLoS One,2018,13(7): e0200343.
[9] Couto JA, Huang AY, Konczyk DJ, et al.Somatic MAP2K1 mutations are associated with extracranial arteriovenous malformation[J]. Am J Hum Genet, 2017, 100(3): 546-554.
[10] Palmieri M, Currò A, Tommasi A, et al.Cell-free DNA next-generation sequencing liquid biopsy as a new revolutionary approach for arteriovenous malformation[J]. JVS Vasc Sci, 2020, 1: 176-180.
[11] Dekeuleneer V, Seront E, Van Damme A, et al.Theranostic advances in vascular malformations[J]. J Invest Dermatol, 2020, 140(4): 756-763.
[12] Smits PJ, Konczyk DJ, Sudduth, CL, et al.Endothelial MAP2K1 mutations in arteriovenous malformation activate the RAS/MAPK pathway[J]. Biochem Biophys Res Commun, 2020, 529(2): 450-454.
[13] Fish JE, Flores Suarez CP, Boudreau E, et al.Somatic gain of KRAS function in the endothelium is sufficient to cause vascular malformations that require MEK but not PI3K signaling[J]. Circ Res, 2020, 127(6): 727-743.
[14] Asadi S.The role of genetic mutations in gene GNAQ in Sturge-Weber syndrome[J]. Open Cell Sig J, 2019, 1(1): 14-18.
[15] Bichsel C, Bischoff J.A somatic missense mutation in GNAQ causes capillary malformation[J].Curr Opin Hematol, 2019, 26(3): 179-184.
[16] Nguyen V, Hochman M, Mihm MC, et al.The pathogenesis of port wine stain and sturge weber syndrome: complex interactions between genetic alterations and aberrant MAPK and PI3K activation[J]. Int J Mol Sci, 2019, 20(9): 2243-2260.
[17] 翟晓玥, 吴瑶, 娄寅,等. 趋化因子CXCL1在增殖期婴幼儿血管瘤组织中表达研究及外源性CXCL1对血管瘤干细胞的影响[J]. 安徽医科大学学报, 2022, 57(9): 1385-1388.
Zhai XY, Wu Y, Lou Y, et al.Study on the expression of chemokine CXCL1 in infantile hemangioma tissues and the effect of exogenous CXCL1 on hemangioma stem cells[J]. Acta Universitatis Medicinalis Anhui, 2022, 57(9): 1385-1388.
[18] Jinnin M, Ishihara T, Boye E, et al.Recent progress in studies of infantile hemangioma[J]. J Dermatol, 2010, 37(11): 283-298.
[19] Khan ZA, Melero-Martin JM, Wu X, et al.Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin[J].Blood, 2006,108(3): 915-921.
[20] Kleinman ME, Tepper OM, Capla JM, et al.Increased circulating AC133+ CD34+ endothelial progenitor cells in children with hemangioma[J]. Lymphat Res Biol, 2003, 1(4): 301-307.
[21] Li HH, Lou Y, Zhang RR, et al.Propranolol accelerats hemangioma stem cell transformation into adipocyte[J]. Ann Plast Surg, 2019, 83(5): e5-e13.
[22] Melero-Martin JM, De Obaldia ME, Kang SY, et al.Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells[J]. Circ Res, 2008, 103(2): 194-202.
[23] Jinnin M, Medici D, Park L, et al.Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma[J]. Nat Med, 2008, 14(11): 1236-1246.
[24] Shibuya M, Claesson-Welsh, L. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis[J]. Exp Cell Res, 2006, 312(5): 549-560.
[25] Kawaguchi A, Kunimoto K, Inaba Y, et al.Distribution analysis of infantile hemangioma or capillary malformation on the head and face in Japanese patients[J]. J Dermatol, 2019, 46(10): 849-852.
[26] Hashimoto A, Kunimoto K, Kawaguchi A, et al.Analysis of onset and clinical characteristics in Japanese patients with infantile hemangioma[J]. Drug Discov Ther, 2021, 15(4): 210-213.
[27] Lim YH, Bacchiocchi A, Qiu J, et al.GNA14 somatic mutation causes congenital and sporadic vascular tumors by MAPK activation[J]. Am J Hum Genet, 2016, 99(2): 443-450.
[28] Lim YH, Fraile C, Antaya RJ, et al.Tufted angioma with associated Kasabach-Merritt phenomenon caused by somatic mutation in GNA14[J]. Pediatr Dermatol, 2019,36(6): 963-964.
[29] Ten Broek RW, Koelsche C, Eijkelenboom A, et al.Kaposiform hemangioendothelioma and tufted angioma-(epi)genetic analysis including genome-wide methylation profiling[J]. Ann Diagn Pathol, 2020,44: 151434.
[30] Venot Q, Blanc T, Rabia SH, et al.Targeted therapy in patients with PIK3CA-related overgrowth syndrome[J]. Nature, 2018, 558(7711): 540-546.
[31] Freixo C, Ferreira V, Martins J, et al.Efficacy and safety of sirolimus in the treatment of vascular anomalies: a systematic review[J]. J Vasc Surg, 2020, 71(1): 318-327.
[32] Wang H, Guo X, Duan Y, et al.Sirolimus as initial therapy for kaposiform hemangioendothelioma and tufted angioma[J]. Pediatr Dermatol, 2018, 35(5): 635-638.

脉管异常的ISSVA分类概要及分子生物学研究进展

Summary of ISSVA classification of vascular anomalies and review of literature in molecular biology

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	闫志伟, 沈艳玲, 郭军, 刘源, 杨霞, 李欢, 冯瑶, 孙沫逸, 杨耀武. 纤维蛋白胶复合平阳霉素栓塞硬化治疗面颈部静脉畸形的实验研究[J]. 中国口腔颌面外科杂志, 2023, 21(4): 340-344.
[2]	郑家伟, 王绪凯, 秦中平, 范新东, 李凯, 杨耀武, 霍然, 刘少华, 赵吉宏, 汪小勇, 周德凯, 刘学键. 口服普萘洛尔治疗婴幼儿血管瘤中国专家共识（2022版）[J]. 中国口腔颌面外科杂志, 2022, 20(4): 313-319.
[3]	邰茂众, 陈涛, 李克雷, 葛春晓, 徐振国, 秦中平. 2种病变内平阳霉素注射方法治疗68例儿童唇面部微囊型淋巴管畸形疗效分析[J]. 中国口腔颌面外科杂志, 2022, 20(3): 268-272.
[4]	庄乾伟, 李芳芳, 孟箭, 顾倩平, 李志萍. 射频消融联合经皮造影DSA引导下聚多卡醇泡沫硬化剂灌注治疗口腔颌面部静脉畸形38例疗效评价[J]. 中国口腔颌面外科杂志, 2022, 20(2): 135-140.
[5]	郑家伟, 赵泽亮, 陈启铭. 婴幼儿血管瘤循证治疗现状[J]. 中国口腔颌面外科杂志, 2022, 20(1): 7-14.
[6]	吴海威, 于淼, 郑家伟. 口腔颌面部静脉畸形诊治：经验与进展[J]. 中国口腔颌面外科杂志, 2021, 19(2): 186-192.
[7]	王杞章, 郑家伟. 口服普萘洛尔治疗婴幼儿增殖期血管瘤:英国儿科皮肤病学会共识及临床指南[J]. 中国口腔颌面外科杂志, 2020, 18(6): 548-552.
[8]	郑家伟. 西罗莫司治疗静脉畸形研究现状[J]. 中国口腔颌面外科杂志, 2020, 18(6): 553-558.
[9]	顾达, 霍然, 徐广琪, 毕见海, 李尚滨. 局部外用β受体阻滞剂治疗婴幼儿血管瘤的临床应用研究进展[J]. 中国口腔颌面外科杂志, 2020, 18(4): 375-380.
[10]	李红, 周昱川, 龚忠诚, 孙杨, 凌彬. 口服普萘洛尔联合外用盐酸倍他洛尔治疗8例眶周高风险婴幼儿血管瘤的疗效和安全性评价[J]. 中国口腔颌面外科杂志, 2020, 18(3): 264-268.
[11]	宋会新, 林春男, 王田友, 付兆臣. 普萘洛尔治疗婴幼儿血管瘤的作用机制研究进展[J]. 中国口腔颌面外科杂志, 2020, 18(2): 182-185.
[12]	靳能皓, 南欣荣, 闫星泉, 李明. 手术结合平阳霉素注射治疗巨舌症1例报告[J]. 中国口腔颌面外科杂志, 2020, 18(2): 190-192.
[13]	刘朝阳, 唐璟, 杨宏宇. 颈上部支气管源性囊肿1例报告及文献复习[J]. 中国口腔颌面外科杂志, 2019, 17(4): 382-384.
[14]	刘学键, 刘志鹏, 武宜雷, 邰茂众. 平阳霉素新剂型瘤体内注射治疗婴幼儿血管瘤203例临床分析[J]. 中国口腔颌面外科杂志, 2019, 17(3): 247-250.
[15]	雷书赞, 汪接兵, 张银喜. 气管切开全麻下无水乙醇栓塞治疗咽喉部静脉畸形20例报道[J]. 中国口腔颌面外科杂志, 2019, 17(1): 74-76.