Shear stress-stimulated endothelial cells induce smooth muscle cell chemotaxis via platelet-derived growth factor-BB and interleukin-1α

被引:73
作者
Dardik, A [1 ]
Yamashita, A [1 ]
Aziz, F [1 ]
Asada, H [1 ]
Sumpio, BE [1 ]
机构
[1] Yale Univ, Sch Med, Boyer Ctr Mol Med, Vasc Surg Sect, New Haven, CT 06519 USA
关键词
D O I
10.1016/j.jvs.2004.11.016
中图分类号
R61 [外科手术学];
学科分类号
摘要
Objective: Vascular smooth muscle cell (SMC) migration is critical to the development of atherosclerosis and neointimal hyperplasia. Hemodynamic forces such as shear stress and cyclic strain stimulate endothelial cell signal-transduction pathways, resulting in the secretion of several factors, including SMC chemoattractants such as platelet-derived growth factor (PDGF). We hypothesized that mechanical forces stimulate endothelial cells to secrete SMC chemoattractants to induce migration via the mitogen-activated protein kinase (MAPK) pathway. Methods. Bovine aortic endothelial cells were exposed to shear stress, cyclic strain, or static conditions for 16 hours. The resulting conditioned medium was used as a SMC chemoattractant in a Boyden chamber. Activation of SMC extracellular signal-regulated protein kinase 1/2 (ERK1/2) was assessed by Western blot analysis. Pathways were inhibited with anti-PDGF-BB or anti-interleukin-1 alpha (IL-1 alpha) antibodies, or the ERK1/2 upstream pathway inhibitor PD98059. Results. Conditioned medium from endothelial cells exposed to shear stress corresponding to arterial levels of shear stress stimulated SMC migration but lower levels of shear stress or cyclic strain did not. Both PDGF-BB and IL-1 alpha were secreted into the conditioned medium by endothelial cells stimulated with shear stress. Both PDGF-BB and IL-1a, stimulated SMC chemotaxis but were not synergistic, and both stimulated SMC ERK1/2 phosphorylation. Inhibition of PDGF-BB or IL-1 alpha inhibited SMC chemotaxis and ERK1/2 phosphorylation. Conclusion: Shear stress stimulates endothelial cells to secrete several SMC chemoattractants, including PDGF-BB and IL-1 alpha; both PDGF-BB and IL-1 alpha stimulate SMC chemotaxis via the ERK1/2 signal-transduction pathway. These results suggest that the response to vascular injury may have a common pathway amenable to pharmacologic manipulation.
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页码:321 / 331
页数:11
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共 62 条
  • [1] SIGNALING MECHANISMS IN THE REGULATION OF VASCULAR CELL-MIGRATION
    ABEDI, H
    ZACHARY, I
    [J]. CARDIOVASCULAR RESEARCH, 1995, 30 (04) : 544 - 556
  • [2] PD-098059 IS A SPECIFIC INHIBITOR OF THE ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE KINASE IN-VITRO AND IN-VIVO
    ALESSI, DR
    CUENDA, A
    COHEN, P
    DUDLEY, DT
    SALTIEL, AR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (46) : 27489 - 27494
  • [3] Endothelial cell response to different mechanical forces
    Azuma, N
    Duzgun, A
    Ikeda, M
    Kito, H
    Akasaka, N
    Sasajima, T
    Sumpio, BE
    [J]. JOURNAL OF VASCULAR SURGERY, 2000, 32 (04) : 789 - 794
  • [4] Temporal gradient in sheer-induced signaling pathway:: involvement of MAP kinase, c-fos, and connexin43
    Bao, XP
    Clark, CB
    Frangos, JA
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2000, 278 (05): : H1598 - H1605
  • [5] INSULIN-LIKE GROWTH-FACTOR-I AND PLATELET-DERIVED GROWTH FACTOR-BB INDUCE DIRECTED MIGRATION OF HUMAN ARTERIAL SMOOTH-MUSCLE CELLS VIA SIGNALING PATHWAYS THAT ARE DISTINCT FROM THOSE OF PROLIFERATION
    BORNFELDT, KE
    RAINES, EW
    NAKANO, T
    GRAVES, LM
    KREBS, EG
    ROSS, R
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (03) : 1266 - 1274
  • [6] The interleukin-1 receptor/Toll-like receptor superfamily: signal generators for pro-inflammatory interleukins and microbial products
    Bowie, A
    O'Neill, LAJ
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 2000, 67 (04) : 508 - 514
  • [7] Effects of mechanical forces on signal transduction and gene expression in endothelial cells
    Chien, S
    Li, S
    Shyy, JYJ
    [J]. HYPERTENSION, 1998, 31 (01) : 162 - 169
  • [8] Nitric oxide regulates shear stress-induced early growth response-1 - Expression via the extracellular signal-regulated kinase pathway in endothelial cells
    Chiu, JJ
    Wung, BS
    Hsieh, HJ
    Lo, LW
    Wang, DL
    [J]. CIRCULATION RESEARCH, 1999, 85 (03) : 238 - 246
  • [9] Interleukin-1/toll receptor family members: Receptor structure and signal transduction pathways
    Daun, JM
    Fenton, MJ
    [J]. JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2000, 20 (10) : 843 - 855
  • [10] FLOW-MEDIATED ENDOTHELIAL MECHANOTRANSDUCTION
    DAVIES, PF
    [J]. PHYSIOLOGICAL REVIEWS, 1995, 75 (03) : 519 - 560