2025年7月13日 周日
首页 > 按月查看>2017年第9月 >865-873
PDF 导出
增龄和高血压经PI3K/Akt和MAPK信号通路间平衡介导调控血管平滑肌细胞的表型转换
作者:
作者单位:

(北京体育大学运动与体质健康实验室,北京市 100084)

作者简介:

张琳,博士研究生,研究方向为运动和心血管生理学,E-mail为zhanglinbus@126.com。

基金项目:

国家自然科学基金项目(31371201)；国家体育总局全民健身领域课题(2015B035)


Aging and hypertension mediate the phenotypic switching of vascular smooth muscle cells through the balance between PI3K/Akt and MAPK signaling pathways
Author:
Affiliation:

Department of Exercise and Physical Health, Beijing Sport University, Beijing 100084, China)

  • 摘要
    • | |
  • 访问统计
    • |
  • 参考文献
    • |
  • 相似文献
    • | |
    摘要:

    目的 探究增龄和高血压对胸主动脉血管平滑肌细胞(VSMC)表型转换的影响及磷脂酰肌醇激酶(PI3K/Akt)和丝裂原活化蛋白激酶(MAPK)信号通路对VSMC表型的调控。 方法 选取1、3、9、16月龄的雄性Wistar Kyoto大鼠(WKY)和自发性高血压大鼠(SHR)各12只,尾动脉无创测定血压,取各组大鼠的胸主动脉进行实验。HE染色测量胸主动脉的管壁厚度；免疫组织化学染色检测VSMC表型标志蛋白α平滑肌肌动蛋白(α-SM-actin)、调宁蛋白、骨桥蛋白(OPN)的表达和分布；Western blot检测VSMC表型标志蛋白α-SM-actin、调宁蛋白、OPN及信号蛋白p-Akt、内皮型一氧化氮合酶(eNOS)、p-42/44ERK、p-p38MAPK的表达量。 结果 HE染色结果显示,增龄导致管壁厚度增加,且在9月龄时WKY和SHR出现显著差异(P＜0.01)。免疫组织化学染色和Western blot结果表明,3月龄后,WKY和SHR的α-SM-actin、调宁蛋白表达量随月龄增加出现下调,而OPN出现上调；p-Akt、eNOS的蛋白表达量随月龄增加逐渐下调,p-42/44ERK、p-p38MAPK蛋白表达量随月龄增长逐渐上调,且3月龄时两组已有显著差异(P＜0.01)。 结论 增龄和高血压均导致大鼠胸主动脉VSMC收缩表型标志蛋白α-SM-actin、调宁蛋白的表达下调,合成表型标志蛋白OPN的表达上调,二者的交互作用更显著。VSMC的表型转换可能是通过PI3K/Akt和MAPK信号通路间的平衡作用进行调控的。

    Abstract:

    Aim To explore the effects of aging and hypertension on phenotypic switching of thoracic aortic vascular smooth muscle cell (VSMC) and regulation of VSMC phenotype by phosphatidylinositol 3-kinase (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling pathway. Methods Male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were studied at 1,3, 9,6 months of age, and each group had 12 rats. Blood pressure was noninvasively measured in the caudal artery. The thoracic aorta of rats in each group was taken for the experiment. HE staining was used to measure the wall thickness of the thoracic aorta. The expression and distribution of VSMC phenotype marker proteins α-smooth muscle-actin (α-SM-actin), calponin and osteopontin (OPN) were detected by immunohistochemical staining. Western blot was used to detect the expression of VSMC phenotype marker protein α-SM-actin, calponin, OPN, and signal proteins p-Akt, endothelial nitric oxide synthase (eNOS), p-42/44ERK and p-p38MAPK. Results HE staining showed that aging resulted in an increase in the thickness of vascular wall, and at 9 months old, there was a significant difference between WKY and SHR (P＜0.01). Immunohistochemical staining and Western blot showed that after 3 months old, the expressions of α-SM-actin and calponin in WKY and SHR decreased with the increase of age, while OPN increased; The expressions of p-Akt and eNOS proteins gradually decreased with the increase of age, and the expressions of p-42/44ERK and p-p38MAPK proteins increased gradually with the increase of age; At 3 months old, there was significant difference between the two groups (P＜0.01). Conclusion Aging and hypertension all contribute to the decreases in expressions of VSMC contractile phenotype marker proteins α-SM-actin and calponin, and the increase in the expression of VSMC synthetic phenotypic marker protein OPN in rat thoracic aorta. The interaction between aging and hypertension is more significant. The phenotypic switching of VSMC may be mediated by the balance between PI3K/Akt and MAPK signaling pathways.

    参考文献
    [1] 姚宗芹, 陈弹, 蒋廷波, 等.继发性高血压的临床特点及诊断分析.四川医学, 0,1(2):179-181.
    [2] Lavigne MC, Ramwell PW, Clarke R.Growth and phenotypic characterization of porcine coronary artery smooth muscle cells.In Vitro Cell Dev Biol Anim, 9,5(3):136-143.
    [3] Beamish JA, He P, Kottke-Marchant K, et al.Molecular regulation of contractile smooth muscle cell phenotype:implications for vascular tissue engineering.Tissue Eng Part B Rev, 0,6(5):467-491.
    [4] Weber GF, Lett GS, Haubein NC.Osteopontin is a marker for cancer aggressiveness and patient survival.Br J Cancer, 0,3(6):861-869.
    [5] Jonker DJ, Karapetis CS, Harbison C, et al.Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer.Br J Cancer, 4,0(3):648-655.
    [6] Gerthoffer WT.Mechanisms of vascular smooth muscle cell migration.Circ Res, 7,0(5):607-621.
    [7] Fan Z, Li C, Qin C, et al.Role of the PI3K/AKT pathway in modulating cytoskeleton rearrangements and phenotype switching in rat pulmonary arterial vascular smooth muscle cells.DNA Cell Biol, 4,3(1):12-19.
    [8] 杨静, 雷燕.细胞衰老与血管老化的关系及其研究进展.中国中西医结合杂志, 9,9(4):369-374.
    [9] Rensen SS, Doevendans PA, van Eys GJ.Regulation and characteristics of vascular smooth muscle cell phenotypic diversity.Neth Heart J, 7,5(3):100-108.
    [10] Sehgel NL, Qiu H, Hunter WC.Hypertension and aging effects on vascular smooth muscle cell contribution to reconstituted aortic tissue elasticity.Bioengineering Conference (NEBEC),2011; 1-2.
    [11] Li Z, Lu N, Shi L.Exercise training reverses alterations in Kv and BKCa channel molecular expression in thoracic aorta smooth muscle cells from spontaneously hypertensive rats.J Vasc Res, 4,1(6):447-457.
    [12] 李玉林, 杨相林.肾性高血压家兔主动脉内膜和中膜结构改变及其与自然老化的关系.老年医学杂志, 2,2(2):9-14.
    [13] 范平, 司军强, 刘政江, 等.自发性高血压大鼠模型的应用研究进展.农垦医学, 4,6(6):444-448.
    [14] 许士凯.衰老理论与心血管系统老化研究进展.实用老年医学, 9,3(3):127-129.
    [15] Sehgel NL, Sun Z, Hong Z, et al.Augmented vascular smooth muscle cell stiffness and adhesion when hypertension is superimposed on aging.Hypertension, 5,5(2):370-377.
    [16] 吴金星, 张钧.原发性高血压对组织因子的影响及其机制的探讨.中华老年心脑血管病杂志, 9,1(2):155-157.
    [17] Fukutomi M, Kario K.Aging and hypertension..Expert Rev Cardiovasc Ther, 0,8(11):1 531-539.
    [18] Chen CH, Ho HH, Wu ML, et al.Modulation of cysteine-rich protein 2 expression in vascular injury and atherosclerosis.Mol Biol Rep, 4,1(11):7 033-041.
    [19] Duband JL, Gimona M, Scatena M, et al.Calponin and SM22 as differentiation markers of smooth muscle:spatiotemporal distribution during avian embryonic development.Differentiation, 3,5(1):1-11.
    [20] Rosenberg M, Zugck C, Nelles M, et al.Osteopontin, a new prognostic biomarker in patients with chronic heart failure.Circ Heart Fail, 8,1(1):43-49.
    [21] Stpień E, Wypasek E, Stopyra K, et al.Increased levels of bone remodeling biomarkers (osteoprotegerin and osteopontin) in hypertensive individuals.Clin Biochem, 1,4(10-11):826-831.
    [22] Rosenberg M, Meyer FJ, Gruenig E, et al.Osteopontin (OPN) improves risk stratification in pulmonary hypertension (PH).Int J Cardiol, 2,5(3):504-505.
    [23] Gao H, Steffen MC, Ramos KS.Osteopontin regulates α-smooth muscle actin and calponin in vascular smooth muscle cells.Cell Biol Int, 2,6(2):155-161.
    [24] Brozovich FV, Nicholson CJ, Degen CV, et al.Mechanisms of vascular smooth muscle contraction and the basis for pharmacologic treatment of smooth muscle disorders.Pharmacol Rev, 6,8(2):476-532.
    [25] Osaki M, Oshimura M, Ito H.PI3K-Akt pathway:its functions and alterations in human cancer.Apoptosis, 4,9(9):667-676.
    [26] Umemoto S, Kawahara S, Hashimoto R, et al.Different effects of amlodipine and enalapril on the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase pathway for induction of vascular smooth muscle cell differentiation in vivo.Hypertens Res, 6,9(3):179-186.
    [27] Zhang YM, Wang KQ, Zhou GM, et al.Endothelin-1 promoted proliferation of vascular smooth muscle cell through pathway of extracellular signal-regulated kinase and cyclin D1.Acta Pharmacol Sin, 3,4(6):563-568.
    [28] Cuenda A, Rousseau S.p38 MAP-kinases pathway regulation, function and role in human diseases.Biochim Biophys Acta, 7,3(8):1 358-375.
    引证文献
引用本文

张琳,廖静雯,吴迎,曾凡星,石丽君.增龄和高血压经PI3K/Akt和MAPK信号通路间平衡介导调控血管平滑肌细胞的表型转换[J].中国动脉硬化杂志,2017,25(9):865~873.

复制
分享
文章指标
  • 点击次数:1129
  • 下载次数: 1025
历史
  • 收稿日期:2016-11-07
  • 最后修改日期:2017-07-10
  • 在线发布日期: 2017-09-29

您是本站第 4936617 访问者

邮编：421001 传真：0734-8160523

电话：0734-8160765 E-mail：dmzzbjb@163.net

中国动脉硬化杂志 ® 2025 网站版权所有