Cellular and Molecular Life Sciences

, Volume 74, Issue 12, pp 2263–2282 | Cite as

Integrin signaling in atherosclerosis

  • Alexandra C. Finney
  • Karen Y. Stokes
  • Christopher B. Pattillo
  • A. Wayne Orr
Review

Abstract

Atherosclerosis, a chronic lipid-driven inflammatory disease affecting large arteries, represents the primary cause of cardiovascular disease in the world. The local remodeling of the vessel intima during atherosclerosis involves the modulation of vascular cell phenotype, alteration of cell migration and proliferation, and propagation of local extracellular matrix remodeling. All of these responses represent targets of the integrin family of cell adhesion receptors. As such, alterations in integrin signaling affect multiple aspects of atherosclerosis, from the earliest induction of inflammation to the development of advanced fibrotic plaques. Integrin signaling has been shown to regulate endothelial phenotype, facilitate leukocyte homing, affect leukocyte function, and drive smooth muscle fibroproliferative remodeling. In addition, integrin signaling in platelets contributes to the thrombotic complications that typically drive the clinical manifestation of cardiovascular disease. In this review, we examine the current literature on integrin regulation of atherosclerotic plaque development and the suitability of integrins as potential therapeutic targets to limit cardiovascular disease and its complications.

Keywords

Integrins Extracellular matrix Atherosclerosis Inflammation Proliferation Migration 

Notes

Acknowledgements

This work was supported by the National Institute of Health (R01 HL098435 to A.W.O.), by an American Heart Association Grant-In-Aid (15GRNT25560056 to A.W.O.), an intramural Malcolm Feist Pre-doctoral Fellowship (to A.C.F.), and an American Heart Association Pre-doctoral Fellowship (17PRE33440111 to A.C.F.).

References

  1. 1.
    Kingsley K et al (2002) ERK1/2 mediates PDGF-BB stimulated vascular smooth muscle cell proliferation and migration on laminin-5. Biochem Biophys Res Commun 293(3):1000–1006PubMedCrossRefGoogle Scholar
  2. 2.
    Chahine MN et al (2009) Oxidized LDL affects smooth muscle cell growth through MAPK-mediated actions on nuclear protein import. J Mol Cell Cardiol 46(3):431–441PubMedCrossRefGoogle Scholar
  3. 3.
    Orr AW et al (2009) Molecular mechanisms of collagen isotype-specific modulation of smooth muscle cell phenotype. Arterioscler Thromb Vasc Biol 29(2):225–231PubMedCrossRefGoogle Scholar
  4. 4.
    Autieri MV (2012) Pro- and anti-inflammatory cytokine networks in atherosclerosis. ISRN Vasc Med 2012:17Google Scholar
  5. 5.
    Owens GK, Kumar MS, Wamhoff BR (2004) Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 84(3):767–801PubMedCrossRefGoogle Scholar
  6. 6.
    Stary HC et al (1995) A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 92(5):1355–1374Google Scholar
  7. 7.
    Virmani R et al (2006) Pathology of the vulnerable plaque. J Am Coll Cardiol 47(8 Suppl):C13–C18PubMedCrossRefGoogle Scholar
  8. 8.
    Libby P (2005) The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol 46(7):1225–1228PubMedCrossRefGoogle Scholar
  9. 9.
    Hahn C, Schwartz MA (2009) Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol 10(1):53–62PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Yurdagul A Jr. et al (2016) The arterial microenvironment: the where and why of atherosclerosis. Biochem J 473(10):1281–1295PubMedCrossRefGoogle Scholar
  11. 11.
    Yurdagul A Jr., Orr AW (2016) Blood brothers: hemodynamics and cell-matrix interactions in endothelial function. Antioxid Redox Signal 25(7):415–434PubMedCrossRefGoogle Scholar
  12. 12.
    Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110(6):673–687PubMedCrossRefGoogle Scholar
  13. 13.
    Ross TD et al (2013) Integrins in mechanotransduction. Curr Opin Cell Biol 25(5):613–618PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Stupack DG, Cheresh DA (2002) ECM remodeling regulates angiogenesis: endothelial integrins look for new ligands. Sci STKE 2002(119):PE7PubMedGoogle Scholar
  15. 15.
    Ley K et al (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7(9):678–689PubMedCrossRefGoogle Scholar
  16. 16.
    Shattil SJ, Ginsberg MH, Brugge JS (1994) Adhesive signaling in platelets. Curr Opin Cell Biol 6(5):695–704PubMedCrossRefGoogle Scholar
  17. 17.
    Schwartz MA (2001) Integrin signaling revisited. Trends Cell Biol 11(12):466–470PubMedCrossRefGoogle Scholar
  18. 18.
    Humphries JD et al (2015) Emerging properties of adhesion complexes: what are they and what do they do? Trends Cell Biol 25(7):388–397PubMedCrossRefGoogle Scholar
  19. 19.
    Parsons JT, Horwitz AR, Schwartz MA (2010) Cell adhesion: integrating cytoskeletal dynamics and cellular tension. Nat Rev Mol Cell Biol 11(9):633–643PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Orr AW et al (2006) Mechanisms of mechanotransduction. Dev Cell 10(1):11–20PubMedCrossRefGoogle Scholar
  21. 21.
    Kanchanawong P et al (2010) Nanoscale architecture of integrin-based cell adhesions. Nature 468(7323):580–584PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Byron A et al (2012) Proteomic analysis of alpha4beta1 integrin adhesion complexes reveals alpha-subunit-dependent protein recruitment. Proteomics 12(13):2107–2114PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Schiller HB et al (2013) beta1- and alphav-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments. Nat Cell Biol 15(6):625–636PubMedCrossRefGoogle Scholar
  24. 24.
    Kuo JC et al (2011) Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for beta-Pix in negative regulation of focal adhesion maturation. Nat Cell Biol 13(4):383–393PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Robertson J et al (2015) Defining the phospho-adhesome through the phosphoproteomic analysis of integrin signalling. Nat Commun 6:6265PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Wickstrom SA et al (2010) The ILK/PINCH/parvin complex: the kinase is dead, long live the pseudokinase!. EMBO J 29(2):281–291PubMedCrossRefGoogle Scholar
  27. 27.
    Kim C, Ye F, Ginsberg MH (2011) Regulation of integrin activation. Annu Rev Cell Dev Biol 27:321–345PubMedCrossRefGoogle Scholar
  28. 28.
    Ye F, Snider AK, Ginsberg MH (2014) Talin and kindlin: the one-two punch in integrin activation. Front Med 8(1):6–16PubMedCrossRefGoogle Scholar
  29. 29.
    Jalali S et al (2001) Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. Proc Natl Acad Sci USA 98(3):1042–1046PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Tzima E et al (2001) Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment. EMBO J 20(17):4639–4647PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Orr AW et al (2005) The subendothelial extracellular matrix modulates NF-kappaB activation by flow: a potential role in atherosclerosis. J Cell Biol 169(1):191–202PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Hynes RO (2012) The evolution of metazoan extracellular matrix. J Cell Biol 196(6):671–679PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Short SM, Talbott GA, Juliano RL (1998) Integrin-mediated signaling events in human endothelial cells. Mol Biol Cell 9(8):1969–1980PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Chen J et al (2015) αβ3 integrins mediate flow-induced NF-κB activation, proinflammatory gene expression, and early atherogenic inflammation. Am J Pathol 185(9):2575–2589PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Feaver RE et al (2010) Atheroprone hemodynamics regulate fibronectin deposition to create positive feedback that sustains endothelial inflammation. Circ Res 106(11):1703–1711PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Green J et al (2014) Flow patterns regulate hyperglycemia-induced subendothelial matrix remodeling during early atherogenesis. Atherosclerosis 232(2):277–284PubMedCrossRefGoogle Scholar
  37. 37.
    Rohwedder I et al (2012) Plasma fibronectin deficiency impedes atherosclerosis progression and fibrous cap formation. EMBO Mol Med 4(7):564–576PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Murphy PA, Hynes RO (2014) Alternative splicing of endothelial fibronectin is induced by disturbed hemodynamics and protects against hemorrhage of the vessel wall. Arterioscler Thromb Vasc Biol 34(9):2042–2050PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Gelfand BD et al (2011) Hemodynamic activation of beta-catenin and T-cell-specific transcription factor signaling in vascular endothelium regulates fibronectin expression. Arterioscler Thromb Vasc Biol 31(7):1625–1633PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    van Keulen JK et al (2007) Levels of extra domain A containing fibronectin in human atherosclerotic plaques are associated with a stable plaque phenotype. Atherosclerosis 195(1):e83–e91PubMedCrossRefGoogle Scholar
  41. 41.
    Pober JS, Sessa WC (2007) Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 7(10):803–815PubMedCrossRefGoogle Scholar
  42. 42.
    Nakashima Y et al (1998) Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. Arterioscler Thromb Vasc Biol 18(5):842–851PubMedCrossRefGoogle Scholar
  43. 43.
    Collins T, Cybulsky MI (2001) NF-kappaB: pivotal mediator or innocent bystander in atherogenesis? J Clin Invest 107(3):255–264PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Hajra L et al (2000) The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci USA 97(16):9052–9057PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Cybulsky MI et al (2001) A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 107(10):1255–1262PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Tzima E et al (2005) A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437(7057):426–431PubMedCrossRefGoogle Scholar
  47. 47.
    Hahn C et al (2009) The subendothelial extracellular matrix modulates JNK activation by flow. Circ Res 104(8):995–1003PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Orr AW et al (2008) p21-activated kinase signaling regulates oxidant-dependent NF-kappa B activation by flow. Circ Res 103(6):671–679PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Orr AW et al (2007) Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis. J Cell Biol 176(5):719–727PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Bhullar IS et al (1998) Fluid shear stress activation of IkappaB kinase is integrin-dependent. J Biol Chem 273(46):30544–30549PubMedCrossRefGoogle Scholar
  51. 51.
    Sun X et al (2016) Activation of integrin alpha5 mediated by flow requires its translocation to membrane lipid rafts in vascular endothelial cells. Proc Natl Acad Sci USA 113(3):769–774PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Yun S et al (2016) Interaction between integrin alpha5 and PDE4D regulates endothelial inflammatory signalling. Nat Cell Biol 18(10):1043–1053PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Yurdagul A Jr. et al (2014) α5β1 integrin signaling mediates oxidized low-density lipoprotein-induced inflammation and early atherosclerosis. Arterioscler Thromb Vasc Biol 34(7):1362–1373PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Yurdagul A Jr. et al (2016) Oxidized LDL induces FAK-dependent RSK signaling to drive NF-kappaB activation and VCAM-1 expression. J Cell Sci 129:1580–1591PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Funk SD, Yurdagul A Jr., Orr AW (2012) Hyperglycemia and endothelial dysfunction in atherosclerosis: lessons from type 1 diabetes. Int J Vasc Med 2012:569654PubMedPubMedCentralGoogle Scholar
  56. 56.
    Pober JS, Min W (2006) Endothelial cell dysfunction, injury and death. Handb Exp Pharmacol 176(Pt 2):135–156CrossRefGoogle Scholar
  57. 57.
    Fleming I (2010) Molecular mechanisms underlying the activation of eNOS. Pflugers Arch 459(6):793–806PubMedCrossRefGoogle Scholar
  58. 58.
    Dimmeler S et al (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399(6736):601–605PubMedCrossRefGoogle Scholar
  59. 59.
    Boo YC et al (2002) Shear stress stimulates phosphorylation of endothelial nitric-oxide synthase at Ser1179 by Akt-independent mechanisms: role of protein kinase A. J Biol Chem 277(5):3388–3396PubMedCrossRefGoogle Scholar
  60. 60.
    Yang B, Rizzo V (2013) Shear stress activates eNOS at the endothelial apical surface through 1 containing integrins and caveolae. Cell Mol Bioeng 6(3):346–354PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Orr AW et al (2006) Matrix-specific suppression of integrin activation in shear stress signaling. Mol Biol Cell 17(11):4686–4697PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Yurdagul A Jr. et al (2013) Altered nitric oxide production mediates matrix-specific PAK2 and NF-kappaB activation by flow. Mol Biol Cell 24(3):398–408PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Funk SD et al (2010) Matrix-specific protein kinase A signaling regulates p21-activated kinase activation by flow in endothelial cells. Circ Res 106(8):1394–1403PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Mulligan-Kehoe MJ, Simons M (2014) Vasa vasorum in normal and diseased arteries. Circulation 129(24):2557–2566PubMedCrossRefGoogle Scholar
  65. 65.
    Annex BH (2013) Therapeutic angiogenesis for critical limb ischaemia. Nat Rev Cardiol 10(7):387–396PubMedCrossRefGoogle Scholar
  66. 66.
    Kwon HM et al (1998) Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia. J Clin Invest 101(8):1551–1556PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Langheinrich AC et al (2006) Correlation of vasa vasorum neovascularization and plaque progression in aortas of apolipoprotein E(-/-)/low-density lipoprotein(-/-) double knockout mice. Arterioscler Thromb Vasc Biol 26(2):347–352PubMedCrossRefGoogle Scholar
  68. 68.
    Moulton KS et al (2003) Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci USA 100(8):4736–4741PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    O’Brien KD et al (1996) Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. Circulation 93(4):672–682PubMedCrossRefGoogle Scholar
  70. 70.
    Moreno PR et al (2004) Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation 110(14):2032–2038PubMedCrossRefGoogle Scholar
  71. 71.
    Virmani R et al (2005) Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol 25(10):2054–2061PubMedCrossRefGoogle Scholar
  72. 72.
    Semenza GL (2014) Hypoxia-inducible factor 1 and cardiovascular disease. Annu Rev Physiol 76:39–56PubMedCrossRefGoogle Scholar
  73. 73.
    Mollmark JI et al (2012) Fibroblast growth factor-2 is required for vasa vasorum plexus stability in hypercholesterolemic mice. Arterioscler Thromb Vasc Biol 32(11):2644–2651PubMedCrossRefGoogle Scholar
  74. 74.
    Hutter R et al (2013) Macrophages transmit potent proangiogenic effects of oxLDL in vitro and in vivo involving HIF-1alpha activation: a novel aspect of angiogenesis in atherosclerosis. J Cardiovasc Transl Res 6(4):558–569PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Jaipersad AS et al (2014) The role of monocytes in angiogenesis and atherosclerosis. J Am Coll Cardiol 63(1):1–11PubMedCrossRefGoogle Scholar
  76. 76.
    Heistad DD, Marcus ML (1979) Role of vasa vasorum in nourishment of the aorta. Blood Vessels 16(5):225–238PubMedGoogle Scholar
  77. 77.
    Moulton KS et al (1999) Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 99(13):1726–1732PubMedCrossRefGoogle Scholar
  78. 78.
    Drinane M et al (2009) The antiangiogenic activity of rPAI-1(23) inhibits vasa vasorum and growth of atherosclerotic plaque. Circ Res 104(3):337–345PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Okamoto E et al (2001) Perivascular inflammation after balloon angioplasty of porcine coronary arteries. Circulation 104(18):2228–2235PubMedCrossRefGoogle Scholar
  80. 80.
    Khurana R et al (2004) Angiogenesis-dependent and independent phases of intimal hyperplasia. Circulation 110(16):2436–2443PubMedCrossRefGoogle Scholar
  81. 81.
    Koga J et al (2009) Soluble Flt-1 gene transfer ameliorates neointima formation after wire injury in flt-1 tyrosine kinase-deficient mice. Arterioscler Thromb Vasc Biol 29(4):458–464PubMedCrossRefGoogle Scholar
  82. 82.
    Ohtani K et al (2004) Blockade of vascular endothelial growth factor suppresses experimental restenosis after intraluminal injury by inhibiting recruitment of monocyte lineage cells. Circulation 110(16):2444–2452PubMedCrossRefGoogle Scholar
  83. 83.
    Robinson SD, Hodivala-Dilke KM (2011) The role of beta3-integrins in tumor angiogenesis: context is everything. Curr Opin Cell Biol 23(5):630–637PubMedCrossRefGoogle Scholar
  84. 84.
    Rehn M et al (2001) Interaction of endostatin with integrins implicated in angiogenesis. Proc Natl Acad Sci USA 98(3):1024–1029PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Xu X et al (2015) Angiogenesis inhibitor, endostar, prevents vasa vasorum neovascularization in a swine atherosclerosis model. J Atheroscler Thromb 22(10):1100–1112PubMedCrossRefGoogle Scholar
  86. 86.
    Brooks PC, Clark RA, Cheresh DA (1994) Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264(5158):569–571PubMedCrossRefGoogle Scholar
  87. 87.
    Kim S et al (2000) Regulation of angiogenesis in vivo by ligation of integrin alpha5beta1 with the central cell-binding domain of fibronectin. Am J Pathol 156(4):1345–1362PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Orbay H et al (2013) Positron emission tomography imaging of atherosclerosis. Theranostics 3(11):894–902PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Hodivala-Dilke KM et al (1999) Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. J Clin Invest 103(2):229–238PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Bader BL et al (1998) Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins. Cell 95(4):507–519PubMedCrossRefGoogle Scholar
  91. 91.
    Reynolds LE et al (2002) Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med 8(1):27–34PubMedCrossRefGoogle Scholar
  92. 92.
    van der Flier A et al (2010) Endothelial alpha5 and alphav integrins cooperate in remodeling of the vasculature during development. Development 137(14):2439–2449PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Murphy PA, Begum S, Hynes RO (2015) Tumor angiogenesis in the absence of fibronectin or its cognate integrin receptors. PLoS One 10(3):e0120872PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Berlin, C., et al (1993) Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 74(1):185–195Google Scholar
  95. 95.
    Libby P, Hansson GK (2015) Inflammation and immunity in diseases of the arterial tree: players and layers. Circ Res 116(2):307–311PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Johnson-Tidey RR et al (1994) Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1. Am J Pathol 144(5):952–961PubMedPubMedCentralGoogle Scholar
  97. 97.
    van der Wal AC et al (1992) Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions. Am J Pathol 141(6):1427–1433PubMedPubMedCentralGoogle Scholar
  98. 98.
    Collins RG et al (2000) P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice. J Exp Med 191(1):189–194PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Dong ZM, Brown AA, Wagner DD (2000) Prominent role of P-selectin in the development of advanced atherosclerosis in ApoE-deficient mice. Circulation 101(19):2290–2295PubMedCrossRefGoogle Scholar
  100. 100.
    Alon R et al (1995) The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. J Cell Biol 128(6):1243–1253PubMedCrossRefGoogle Scholar
  101. 101.
    Zarbock A, Lowell CA, Ley K (2007) Spleen tyrosine kinase Syk is necessary for E-selectin-induced alpha(L)beta(2) integrin-mediated rolling on intercellular adhesion molecule-1. Immunity 26(6):773–783PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Shamri R et al (2005) Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines. Nat Immunol 6(5):497–506PubMedCrossRefGoogle Scholar
  103. 103.
    Boring L et al (1998) Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394(6696):894–897PubMedCrossRefGoogle Scholar
  104. 104.
    Gu L et al (1998) Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 2(2):275–281PubMedCrossRefGoogle Scholar
  105. 105.
    Braunersreuther V et al (2007) Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice. Arterioscler Thromb Vasc Biol 27(2):373–379PubMedCrossRefGoogle Scholar
  106. 106.
    Braunersreuther V et al (2008) A novel RANTES antagonist prevents progression of established atherosclerotic lesions in mice. Arterioscler Thromb Vasc Biol 28(6):1090–1096PubMedCrossRefGoogle Scholar
  107. 107.
    Combadiere C et al (2003) Decreased atherosclerotic lesion formation in CX3CR1/apolipoprotein E double knockout mice. Circulation 107(7):1009–1016PubMedCrossRefGoogle Scholar
  108. 108.
    Lesnik P, Haskell CA, Charo IF (2003) Decreased atherosclerosis in CX3CR1-/- mice reveals a role for fractalkine in atherogenesis. J Clin Invest 111(3):333–340PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Funk SD, Orr AW (2013) Ephs and ephrins resurface in inflammation, immunity, and atherosclerosis. Pharmacol Res 67(1):42–52PubMedCrossRefGoogle Scholar
  110. 110.
    Braun J et al (2011) Endothelial cell ephrinB2-dependent activation of monocytes in arteriosclerosis. Arterioscler Thromb Vasc Biol 31(2):297–305PubMedCrossRefGoogle Scholar
  111. 111.
    Jellinghaus S et al (2013) Ephrin-A1/EphA4-mediated adhesion of monocytes to endothelial cells. Biochim Biophys Acta 1833(10):2201–2211PubMedCrossRefGoogle Scholar
  112. 112.
    Saeki N et al (2015) EphA2 promotes cell adhesion and spreading of monocyte and monocyte/macrophage cell lines on integrin ligand-coated surfaces. Cell Adh Migr 9(6):469–482PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Poitz DM et al (2015) EphrinB2/EphA4-mediated activation of endothelial cells increases monocyte adhesion. Mol Immunol 68(2 Pt C):648–656PubMedCrossRefGoogle Scholar
  114. 114.
    Funk SD et al (2012) EphA2 activation promotes the endothelial cell inflammatory response: a potential role in atherosclerosis. Arterioscler Thromb Vasc Biol 32(3):686–695PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    van Gils JM et al (2013) Endothelial expression of guidance cues in vessel wall homeostasis dysregulation under proatherosclerotic conditions. Arterioscler Thromb Vasc Biol 33(5):911–919PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Nageh MF et al (1997) Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice. Arterioscler Thromb Vasc Biol 17(8):1517–1520PubMedCrossRefGoogle Scholar
  117. 117.
    Bourdillon MC et al (2000) ICAM-1 deficiency reduces atherosclerotic lesions in double-knockout mice (ApoE(-/-)/ICAM-1(-/-)) fed a fat or a chow diet. Arterioscler Thromb Vasc Biol 20(12):2630–2635PubMedCrossRefGoogle Scholar
  118. 118.
    Arnaout MA (2016) Biology and structure of leukocyte beta 2 integrins and their role in inflammation. F1000Res. doi: 10.12688/f1000research.9415.1 PubMedPubMedCentralGoogle Scholar
  119. 119.
    Sadhu C et al (2007) CD11c/CD18: novel ligands and a role in delayed-type hypersensitivity. J Leukoc Biol 81(6):1395–1403PubMedCrossRefGoogle Scholar
  120. 120.
    Huo Y, Hafezi-Moghadam A, Ley K (2000) Role of vascular cell adhesion molecule-1 and fibronectin connecting segment-1 in monocyte rolling and adhesion on early atherosclerotic lesions. Circ Res 87(2):153–159PubMedCrossRefGoogle Scholar
  121. 121.
    Barringhaus KG et al (2004) Alpha4beta1 integrin (VLA-4) blockade attenuates both early and late leukocyte recruitment and neointimal growth following carotid injury in apolipoprotein E (−/−) mice. J Vasc Res 41(3):252–260PubMedCrossRefGoogle Scholar
  122. 122.
    Yang JT, Rayburn H, Hynes RO (1995) Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development. Development 121(2):549–560PubMedGoogle Scholar
  123. 123.
    Shih PT et al (1999) Minimally modified low-density lipoprotein induces monocyte adhesion to endothelial connecting segment-1 by activating beta1 integrin. J Clin Invest 103(5):613–625PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Merched A, Tollefson K, Chan L (2010) Beta2 integrins modulate the initiation and progression of atherosclerosis in low-density lipoprotein receptor knockout mice. Cardiovasc Res 85(4):853–863PubMedCrossRefGoogle Scholar
  125. 125.
    Nie Q et al (1997) Inhibition of mononuclear cell recruitment in aortic intima by treatment with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies in hypercholesterolemic rats: implications of the ICAM-1 and LFA-1 pathway in atherogenesis. Lab Invest 77(5):469–482PubMedGoogle Scholar
  126. 126.
    Kawamura A et al (2007) Apolipoprotein E interrupts interleukin-1beta signaling in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 27(7):1610–1617PubMedCrossRefGoogle Scholar
  127. 127.
    Kubo N et al (2000) Leukocyte CD11b expression is not essential for the development of atherosclerosis in mice. J Lipid Res 41(7):1060–1066PubMedGoogle Scholar
  128. 128.
    Wu H et al (2009) Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia. Circulation 119(20):2708–2717PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Hogg N et al (1986) The p150, 95 molecule is a marker of human mononuclear phagocytes: comparison with expression of class II molecules. Eur J Immunol 16(3):240–248PubMedCrossRefGoogle Scholar
  130. 130.
    Blackford J et al (1996) A monoclonal antibody, 3/22, to rabbit CD11c which induces homotypic T cell aggregation: evidence that ICAM-1 is a ligand for CD11c/CD18. Eur J Immunol 26(3):525–531PubMedCrossRefGoogle Scholar
  131. 131.
    Loike JD et al (1991) CD11c/CD18 on neutrophils recognizes a domain at the N terminus of the A alpha chain of fibrinogen. Proc Natl Acad Sci USA 88(3):1044–1048PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Foster GA et al (2015) CD11c/CD18 signals very late antigen-4 activation to initiate foamy monocyte recruitment during the onset of hypercholesterolemia. J Immunol 195(11):5380–5392PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Gower RM et al (2011) CD11c/CD18 expression is upregulated on blood monocytes during hypertriglyceridemia and enhances adhesion to vascular cell adhesion molecule-1. Arterioscler Thromb Vasc Biol 31(1):160–166PubMedCrossRefGoogle Scholar
  134. 134.
    Han J et al (2006) Reconstructing and deconstructing agonist-induced activation of integrin alphaIIbbeta3. Curr Biol 16(18):1796–1806PubMedCrossRefGoogle Scholar
  135. 135.
    Boulaftali Y et al (2016) CalDAG-GEFI deficiency reduces atherosclerotic lesion development in mice. Arterioscler Thromb Vasc Biol 36:792–799PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Moser M et al (2009) Kindlin-3 is required for beta2 integrin-mediated leukocyte adhesion to endothelial cells. Nat Med 15(3):300–305PubMedCrossRefGoogle Scholar
  137. 137.
    Malinin NL et al (2009) A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. Nat Med 15(3):313–318PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Hyduk SJ et al (2011) Talin-1 and kindlin-3 regulate alpha4beta1 integrin-mediated adhesion stabilization, but not G protein-coupled receptor-induced affinity upregulation. J Immunol 187(8):4360–4368PubMedCrossRefGoogle Scholar
  139. 139.
    Becker HM et al (2013) Alpha1beta1 integrin-mediated adhesion inhibits macrophage exit from a peripheral inflammatory lesion. J Immunol 190(8):4305–4314PubMedCrossRefGoogle Scholar
  140. 140.
    Antonov AS et al (2004) Regulation of macrophage foam cell formation by alphaVbeta3 integrin: potential role in human atherosclerosis. Am J Pathol 165(1):247–258PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Prieto J, Eklund A, Patarroyo M (1994) Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages. Cell Immunol 156(1):191–211PubMedCrossRefGoogle Scholar
  142. 142.
    De Nichilo MO, Yamada KM (1996) Integrin alpha v beta 5-dependent serine phosphorylation of paxillin in cultured human macrophages adherent to vitronectin. J Biol Chem 271(18):11016–11022PubMedCrossRefGoogle Scholar
  143. 143.
    Ammon C et al (2000) Comparative analysis of integrin expression on monocyte-derived macrophages and monocyte-derived dendritic cells. Immunology 100(3):364–369PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Schapira K et al (2005) Genetic deletion or antibody blockade of alpha1beta1 integrin induces a stable plaque phenotype in ApoE−/− mice. Arterioscler Thromb Vasc Biol 25(9):1917–1924PubMedCrossRefGoogle Scholar
  145. 145.
    Lund SA et al., Osteopontin mediates macrophage chemotaxis via alpha(4) and alpha(9) integrins and survival via the alpha(4) integrin. J Cell Biochem, 2012Google Scholar
  146. 146.
    Yakubenko VP, Yadav SP, Ugarova TP (2006) Integrin alphaDbeta2, an adhesion receptor up-regulated on macrophage foam cells, exhibits multiligand-binding properties. Blood 107(4):1643–1650PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Yakubenko VP et al (2008) The role of integrin alpha D beta2 (CD11d/CD18) in monocyte/macrophage migration. Exp Cell Res 314(14):2569–2578PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Lishko VK, Yakubenko VP, Ugarova TP (2003) The interplay between integrins alphaMbeta2 and alpha5beta1 during cell migration to fibronectin. Exp Cell Res 283(1):116–126PubMedCrossRefGoogle Scholar
  149. 149.
    Yakubenko VP et al (2011) Alphambeta(2) integrin activation prevents alternative activation of human and murine macrophages and impedes foam cell formation. Circ Res 108(5):544–554PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Gray JL, Shankar R (1995) Down regulation of CD11b and CD18 expression in atherosclerotic lesion-derived macrophages. Am Surg 61(8):674-679 (discussion 679–80)Google Scholar
  151. 151.
    Zhi K et al (2014) Alpha4beta7 Integrin (LPAM-1) is upregulated at atherosclerotic lesions and is involved in atherosclerosis progression. Cell Physiol Biochem 33(6):1876–1887PubMedCrossRefGoogle Scholar
  152. 152.
    Antonov AS et al (2011) AlphaVbeta3 integrin regulates macrophage inflammatory responses via PI3 kinase/Akt-dependent NF-kappaB activation. J Cell Physiol 226(2):469–476PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Schneider JG et al (2007) Macrophage beta3 integrin suppresses hyperlipidemia-induced inflammation by modulating TNFalpha expression. Arterioscler Thromb Vasc Biol 27(12):2699–2706PubMedCrossRefGoogle Scholar
  154. 154.
    Lacy-Hulbert A et al (2007) Ulcerative colitis and autoimmunity induced by loss of myeloid alphav integrins. Proc Natl Acad Sci USA 104(40):15823–15828PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Poon IK et al (2014) Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol 14(3):166–180PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    Savill J et al (1990) Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature 343(6254):170–173PubMedCrossRefGoogle Scholar
  157. 157.
    Hanayama R et al (2004) Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304(5674):1147–1150PubMedCrossRefGoogle Scholar
  158. 158.
    Friggeri A et al (2010) HMGB1 inhibits macrophage activity in efferocytosis through binding to the alphavbeta3-integrin. Am J Physiol Cell Physiol 299(6):C1267–C1276PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Fan Z et al (2016) HMGB1: a promising therapeutic approach for atherosclerosis. Int J Cardiol 202:507–508PubMedCrossRefGoogle Scholar
  160. 160.
    Wall VZ, Bornfeldt KE (2014) Arterial smooth muscle. Arterioscler Thromb Vasc Biol 34(10):2175–2179PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Hedin U et al (1988) Diverse effects of fibronectin and laminin on phenotypic properties of cultured arterial smooth muscle cells. J Cell Biol 107(1):307–319PubMedCrossRefGoogle Scholar
  162. 162.
    Orr AW et al (2010) Complex regulation and function of the inflammatory smooth muscle cell phenotype in atherosclerosis. J Vasc Res 47(2):168–180PubMedCrossRefGoogle Scholar
  163. 163.
    Vengrenyuk Y et al (2015) Cholesterol loading reprograms the microRNA-143/145-myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype. Arterioscler Thromb Vasc Biol 35(3):535–546PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Shankman LS et al (2015) KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nat Med 21(6):628–637PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Voss B, Rauterberg J (1986) Localization of collagen types I, III, IV and V, fibronectin and laminin in human arteries by the indirect immunofluorescence method. Pathol Res Pract 181(5):568–575PubMedCrossRefGoogle Scholar
  166. 166.
    Moiseeva EP (2001) Adhesion receptors of vascular smooth muscle cells and their functions. Cardiovasc Res 52(3):372–386PubMedCrossRefGoogle Scholar
  167. 167.
    Heino J (2000) The collagen receptor integrins have distinct ligand recognition and signaling functions. Matrix Biol 19(4):319–323PubMedCrossRefGoogle Scholar
  168. 168.
    Obata H et al (1997) Smooth muscle cell phenotype-dependent transcriptional regulation of the alpha1 integrin gene. J Biol Chem 272(42):26643–26651PubMedCrossRefGoogle Scholar
  169. 169.
    Cremona O et al (1994) The alpha6 and beta4 integrin subunits are expressed by smooth muscle cells of human small vessels: a new localization in mesenchymal cells. J Histochem Cytochem 42(9):1221–1228PubMedCrossRefGoogle Scholar
  170. 170.
    Yao CC et al (1997) Functional expression of the alpha 7 integrin receptor in differentiated smooth muscle cells. J Cell Sci 110(Pt 13):1477–1487PubMedGoogle Scholar
  171. 171.
    Wang L et al (2010) Cartilage oligomeric matrix protein maintains the contractile phenotype of vascular smooth muscle cells by interacting with alpha(7)beta(1) integrin. Circ Res 106(3):514–525PubMedCrossRefGoogle Scholar
  172. 172.
    Welser JV et al (2007) Loss of the alpha7 integrin promotes extracellular signal-regulated kinase activation and altered vascular remodeling. Circ Res 101(7):672–681PubMedCrossRefGoogle Scholar
  173. 173.
    Blindt R et al (2002) Expression patterns of integrins on quiescent and invasive smooth muscle cells and impact on cell locomotion. J Mol Cell Cardiol 34(12):1633–1644PubMedCrossRefGoogle Scholar
  174. 174.
    Hoshiga M et al (1995) Alpha-v beta-3 integrin expression in normal and atherosclerotic artery. Circ Res 77(6):1129–1135PubMedCrossRefGoogle Scholar
  175. 175.
    van der Zee R et al (1998) Reduced intimal thickening following alpha(v)beta3 blockade is associated with smooth muscle cell apoptosis. Cell Adhes Commun 6(5):371–379PubMedCrossRefGoogle Scholar
  176. 176.
    Janat MF, Argraves WS, Liau G (1992) Regulation of vascular smooth muscle cell integrin expression by transforming growth factor beta1 and by platelet-derived growth factor-BB. J Cell Physiol 151(3):588–595PubMedCrossRefGoogle Scholar
  177. 177.
    Brown SL et al (1994) Stimulation of migration of human aortic smooth muscle cells by vitronectin: implications for atherosclerosis. Cardiovasc Res 28(12):1815–1820PubMedCrossRefGoogle Scholar
  178. 178.
    Liu J et al (2014) Oxidized low-density lipoprotein increases the proliferation and migration of human coronary artery smooth muscle cells through the upregulation of osteopontin. Int J Mol Med 33(5):1341–1347PubMedGoogle Scholar
  179. 179.
    Yamamoto K et al (2005) Tenascin-C is an essential factor for neointimal hyperplasia after aortotomy in mice. Cardiovasc Res 65(3):737–742PubMedCrossRefGoogle Scholar
  180. 180.
    Ishigaki T et al (2011) Tenascin-C enhances crosstalk signaling of integrin alphavbeta3/PDGFR-beta complex by SRC recruitment promoting PDGF-induced proliferation and migration in smooth muscle cells. J Cell Physiol 226(10):2617–2624PubMedCrossRefGoogle Scholar
  181. 181.
    Choi ET et al (1994) Inhibition of neointimal hyperplasia by blocking alpha V beta 3 integrin with a small peptide antagonist GpenGRGDSPCA. J Vasc Surg 19(1):125–134PubMedCrossRefGoogle Scholar
  182. 182.
    Bishop GG et al (2001) Selective alpha(v)beta(3)-receptor blockade reduces macrophage infiltration and restenosis after balloon angioplasty in the atherosclerotic rabbit. Circulation 103(14):1906–1911PubMedCrossRefGoogle Scholar
  183. 183.
    Weng S et al (2003) Beta3 integrin deficiency promotes atherosclerosis and pulmonary inflammation in high-fat-fed, hyperlipidemic mice. Proc Natl Acad Sci USA 100(11):6730–6735PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Panchatcharam M et al (2010) Enhanced proliferation and migration of vascular smooth muscle cells in response to vascular injury under hyperglycemic conditions is controlled by beta3 integrin signaling. Int J Biochem Cell Biol 42(6):965–974PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Li G et al (2010) Periostin mediates vascular smooth muscle cell migration through the integrins alphavbeta3 and alphavbeta5 and focal adhesion kinase (FAK) pathway. Atherosclerosis 208(2):358–365PubMedCrossRefGoogle Scholar
  186. 186.
    Schaller MD (2001) Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim Biophys Acta 1540(1):1–21PubMedCrossRefGoogle Scholar
  187. 187.
    Moiseeva EP et al (2003) Galectin-1 interacts with beta-1 subunit of integrin. Biochem Biophys Res Commun 310(3):1010–1016PubMedCrossRefGoogle Scholar
  188. 188.
    Lee BH et al (2006) Betaig-h3 triggers signaling pathways mediating adhesion and migration of vascular smooth muscle cells through alphavbeta5 integrin. Exp Mol Med 38(2):153–161PubMedCrossRefGoogle Scholar
  189. 189.
    Taylor JM et al (2001) Selective expression of an endogenous inhibitor of FAK regulates proliferation and migration of vascular smooth muscle cells. Mol Cell Biol 21(5):1565–1572PubMedPubMedCentralCrossRefGoogle Scholar
  190. 190.
    Maile LA et al (2010) A monoclonal antibody against alphaVbeta3 integrin inhibits development of atherosclerotic lesions in diabetic pigs. Sci Transl Med 2(18):18ra11PubMedPubMedCentralCrossRefGoogle Scholar
  191. 191.
    Zheng B, Clemmons DR (1998) Blocking ligand occupancy of the alphaVbeta3 integrin inhibits insulin-like growth factor I signaling in vascular smooth muscle cells. Proc Natl Acad Sci USA 95(19):11217–11222PubMedPubMedCentralCrossRefGoogle Scholar
  192. 192.
    Hong Z et al (2012) Coordination of fibronectin adhesion with contraction and relaxation in microvascular smooth muscle. Cardiovasc Res 96(1):73–80PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    Hong Z et al (2015) Vascular smooth muscle cell stiffness and adhesion to collagen I modified by vasoactive agonists. PLoS One 10(3):e0119533PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Kappert K et al (2000) Angiotensin II and PDGF-BB stimulate beta(1)-integrin-mediated adhesion and spreading in human VSMCs. Hypertension 35(1 Pt 2):255–261PubMedCrossRefGoogle Scholar
  195. 195.
    Bunni MA et al (2011) Role of integrins in angiotensin II-induced proliferation of vascular smooth muscle cells. Am J Physiol Cell Physiol 300(3):C647–C656PubMedCrossRefGoogle Scholar
  196. 196.
    Tamura K et al (2001) Synergistic interaction of integrin and angiotensin II in activation of extracellular signal-regulated kinase pathways in vascular smooth muscle cells. J Cardiovasc Pharmacol 38(Suppl 1):S59–S62PubMedCrossRefGoogle Scholar
  197. 197.
    Montezano AC et al (2014) Angiotensin II and vascular injury. Curr Hypertens Rep 16(6):431PubMedCrossRefGoogle Scholar
  198. 198.
    Schnapp LM et al (1998) Integrins inhibit angiotensin II-induced contraction in rat aortic rings. Regul Pept 77(1–3):177–183PubMedCrossRefGoogle Scholar
  199. 199.
    Louis H et al (2007) Role of alpha1beta1-integrin in arterial stiffness and angiotensin-induced arterial wall hypertrophy in mice. Am J Physiol Heart Circ Physiol 293(4):H2597–H2604PubMedCrossRefGoogle Scholar
  200. 200.
    Moraes JA et al (2015) Alpha1beta1 and integrin-linked kinase interact and modulate angiotensin II effects in vascular smooth muscle cells. Atherosclerosis 243(2):477–485PubMedCrossRefGoogle Scholar
  201. 201.
    Brassard P et al (2006) Role of angiotensin type-1 and angiotensin type-2 receptors in the expression of vascular integrins in angiotensin II-infused rats. Hypertension 47(1):122–127PubMedCrossRefGoogle Scholar
  202. 202.
    Li S et al (2003) Vascular smooth muscle cells orchestrate the assembly of type I collagen via alpha2beta1 integrin, RhoA, and fibronectin polymerization. Am J Pathol 163(3):1045–1056PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Polte TR, Naftilan AJ, Hanks SK (1994) Focal adhesion kinase is abundant in developing blood vessels and elevation of its phosphotyrosine content in vascular smooth muscle cells is a rapid response to angiotensin II. J Cell Biochem 55(1):106–119PubMedCrossRefGoogle Scholar
  204. 204.
    Zhang F et al (2016) Angiotensin-(1–7) abrogates angiotensin II-induced proliferation, migration and inflammation in VSMCs through inactivation of ROS-mediated PI3K/Akt and MAPK/ERK signaling pathways. Sci Rep 6:34621PubMedPubMedCentralCrossRefGoogle Scholar
  205. 205.
    Blaschke F et al (2002) Angiotensin II-augmented migration of VSMCs towards PDGF-BB involves Pyk2 and ERK 1/2 activation. Basic Res Cardiol 97(4):334–342PubMedCrossRefGoogle Scholar
  206. 206.
    Taniyama Y et al (2003) Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions. Mol Cell Biol 23(22):8019–8029PubMedPubMedCentralCrossRefGoogle Scholar
  207. 207.
    Ishida T et al (1999) Agonist-stimulated cytoskeletal reorganization and signal transduction at focal adhesions in vascular smooth muscle cells require c-Src. J Clin Invest 103(6):789–797PubMedPubMedCentralCrossRefGoogle Scholar
  208. 208.
    Zargham R, Pepin J, Thibault G (2007) Alpha8beta1 Integrin is up-regulated in the neointima concomitant with late luminal loss after balloon injury. Cardiovasc Pathol 16(4):212–220PubMedCrossRefGoogle Scholar
  209. 209.
    Zargham R, Thibault G (2006) Alpha 8 integrin expression is required for maintenance of the smooth muscle cell differentiated phenotype. Cardiovasc Res 71(1):170–178PubMedCrossRefGoogle Scholar
  210. 210.
    Zargham R, Thibault G (2005) Alpha8beta1 Integrin expression in the rat carotid artery: involvement in smooth muscle cell migration and neointima formation. Cardiovasc Res 65(4):813–822PubMedCrossRefGoogle Scholar
  211. 211.
    Zargham R, Touyz RM, Thibault G (2007) Alpha 8 Integrin overexpression in de-differentiated vascular smooth muscle cells attenuates migratory activity and restores the characteristics of the differentiated phenotype. Atherosclerosis 195(2):303–312PubMedCrossRefGoogle Scholar
  212. 212.
    Menendez-Castro C et al (2015) Under-expression of alpha8 integrin aggravates experimental atherosclerosis. J Pathol 236(1):5–16PubMedCrossRefGoogle Scholar
  213. 213.
    Hou G et al (2000) Type VIII collagen stimulates smooth muscle cell migration and matrix metalloproteinase synthesis after arterial injury. Am J Pathol 156(2):467–476PubMedPubMedCentralCrossRefGoogle Scholar
  214. 214.
    Adiguzel E et al (2006) Migration and growth are attenuated in vascular smooth muscle cells with type VIII collagen-null alleles. Arterioscler Thromb Vasc Biol 26(1):56–61PubMedCrossRefGoogle Scholar
  215. 215.
    Hollenbeck ST et al (2004) Type I collagen synergistically enhances PDGF-induced smooth muscle cell proliferation through pp60src-dependent crosstalk between the alpha2beta1 integrin and PDGFbeta receptor. Biochem Biophys Res Commun 325(1):328–337PubMedCrossRefGoogle Scholar
  216. 216.
    Chung CH et al (2009) The integrin alpha(2)beta(1) agonist, aggretin, promotes proliferation and migration of VSMC through NF-kB translocation and PDGF production. Br J Pharmacol 156:846–856PubMedPubMedCentralCrossRefGoogle Scholar
  217. 217.
    Lopes J et al (2013) Type VIII collagen mediates vessel wall remodeling after arterial injury and fibrous cap formation in atherosclerosis. Am J Pathol 182(6):2241–2253PubMedPubMedCentralCrossRefGoogle Scholar
  218. 218.
    Pickering JG et al (2000) Alpha5beta1 integrin expression and luminal edge fibronectin matrix assembly by smooth muscle cells after arterial injury. Am J Pathol 156(2):453–465PubMedPubMedCentralCrossRefGoogle Scholar
  219. 219.
    Mao Y, Schwarzbauer JE (2005) Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol 24(6):389–399PubMedCrossRefGoogle Scholar
  220. 220.
    Frontini MJ et al (2009) Lipid incorporation inhibits Src-dependent assembly of fibronectin and type I collagen by vascular smooth muscle cells. Circ Res 104(7):832–841PubMedCrossRefGoogle Scholar
  221. 221.
    Cheng J et al (2007) Mechanical stretch inhibits oxidized low density lipoprotein-induced apoptosis in vascular smooth muscle cells by up-regulating integrin alphavbeta3 and stablization of PINCH-1. J Biol Chem 282(47):34268–34275PubMedCrossRefGoogle Scholar
  222. 222.
    Ikari Y, Yee KO, Schwartz SM (2000) Role of alpha5beta1 and alphavbeta3 integrins on smooth muscle cell spreading and migration in fibrin gels. Thromb Haemost 84(4):701–705PubMedGoogle Scholar
  223. 223.
    Massberg S et al (2002) A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 196(7):887–896PubMedPubMedCentralCrossRefGoogle Scholar
  224. 224.
    Belton OA et al (2003) Cyclooxygenase isoforms and platelet vessel wall interactions in the apolipoprotein E knockout mouse model of atherosclerosis. Circulation 108(24):3017–3023PubMedCrossRefGoogle Scholar
  225. 225.
    Gawaz M et al (1997) Vitronectin receptor (alpha(v)beta3) mediates platelet adhesion to the luminal aspect of endothelial cells: implications for reperfusion in acute myocardial infarction. Circulation 96(6):1809–1818PubMedCrossRefGoogle Scholar
  226. 226.
    Evangelista V et al (2003) Role of P-selectin, beta2-integrins, and Src tyrosine kinases in mouse neutrophil-platelet adhesion. J Thromb Haemost 1(5):1048–1054PubMedCrossRefGoogle Scholar
  227. 227.
    Neumann FJ et al (1999) Effect of glycoprotein IIb/IIIa receptor blockade on platelet-leukocyte interaction and surface expression of the leukocyte integrin Mac-1 in acute myocardial infarction. J Am Coll Cardiol 34(5):1420–1426PubMedCrossRefGoogle Scholar
  228. 228.
    Patko Z et al (2012) Roles of Mac-1 and glycoprotein IIb/IIIa integrins in leukocyte-platelet aggregate formation: stabilization by Mac-1 and inhibition by GpIIb/IIIa blockers. Platelets 23(5):368–375PubMedCrossRefGoogle Scholar
  229. 229.
    Weber C, Springer TA (1997) Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor. J Clin Invest 100(8):2085–2093PubMedPubMedCentralCrossRefGoogle Scholar
  230. 230.
    Sreeramkumar V et al (2014) Neutrophils scan for activated platelets to initiate inflammation. Science 346(6214):1234–1238PubMedPubMedCentralCrossRefGoogle Scholar
  231. 231.
    von Hundelshausen P et al (2001) RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium. Circulation 103(13):1772–1777CrossRefGoogle Scholar
  232. 232.
    van Gils JM et al (2008) Transendothelial migration drives dissociation of plateletmonocyte complexes. Thromb Haemost 100(2):271–279PubMedGoogle Scholar
  233. 233.
    Fernandez-Patron C et al (1999) Differential regulation of platelet aggregation by matrix metalloproteinases-9 and – 2. Thromb Haemost 82(6):1730–1735PubMedGoogle Scholar
  234. 234.
    Sawicki G et al (1997) Release of gelatinase A during platelet activation mediates aggregation. Nature 386(6625):616–619PubMedCrossRefGoogle Scholar
  235. 235.
    May AE et al (2002) Engagement of glycoprotein IIb/IIIa (alpha(IIb)beta3) on platelets upregulates CD40L and triggers CD40L-dependent matrix degradation by endothelial cells. Circulation 106(16):2111–2117PubMedCrossRefGoogle Scholar
  236. 236.
    Nannizzi-Alaimo L, Alves VL, Phillips DR (2003) Inhibitory effects of glycoprotein IIb/IIIa antagonists and aspirin on the release of soluble CD40 ligand during platelet stimulation. Circulation 107(8):1123–1128PubMedCrossRefGoogle Scholar
  237. 237.
    Lievens D et al (2010) Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis. Blood 116(20):4317–4327PubMedPubMedCentralCrossRefGoogle Scholar
  238. 238.
    Simic D et al (2015) Blocking alpha5beta1 integrin attenuates sCD40L-mediated platelet activation. Clin Appl Thromb HemostGoogle Scholar
  239. 239.
    Santoro SA (1986) Identification of a 160,000 dalton platelet membrane protein that mediates the initial divalent cation-dependent adhesion of platelets to collagen. Cell 46(6):913–920PubMedCrossRefGoogle Scholar
  240. 240.
    Ruggeri ZM (2009) Platelet adhesion under flow. Microcirculation 16(1):58–83PubMedPubMedCentralCrossRefGoogle Scholar
  241. 241.
    Sims PJ et al (1989) Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. J Biol Chem 264(29):17049–17057PubMedGoogle Scholar
  242. 242.
    Hughes PE, Pfaff M (1998) Integrin affinity modulation. Trends Cell Biol 8(9):359–364PubMedCrossRefGoogle Scholar
  243. 243.
    Mastenbroek TG et al (2015) Acute and persistent platelet and coagulant activities in atherothrombosis. J Thromb Haemost 13(Suppl 1):S272–S280Google Scholar
  244. 244.
    Hechler B, Gachet C Comparison of two murine models of thrombosis induced by atherosclerotic plaque injury. Thromb Haemost 105(Suppl 1):S3–S12Google Scholar
  245. 245.
    Goto S et al (2002) Involvement of glycoprotein VI in platelet thrombus formation on both collagen and von Willebrand factor surfaces under flow conditions. Circulation 106(2):266–272PubMedCrossRefGoogle Scholar
  246. 246.
    Nesbitt WS et al (2009) A shear gradient-dependent platelet aggregation mechanism drives thrombus formation. Nat Med 15(6):665–673PubMedCrossRefGoogle Scholar
  247. 247.
    Collins C et al (2014) Haemodynamic and extracellular matrix cues regulate the mechanical phenotype and stiffness of aortic endothelial cells. Nat Commun 5:3984PubMedPubMedCentralGoogle Scholar
  248. 248.
    Kawamura A et al (2004) Increased expression of monocyte CD11a and intracellular adhesion molecule-1 in patients with initial atherosclerotic coronary stenosis. Circ J 68(1):6–10PubMedCrossRefGoogle Scholar
  249. 249.
    Skinner MP, Raines EW, Ross R (1994) Dynamic expression of alpha 1 beta 1 and alpha 2 beta 1 integrin receptors by human vascular smooth muscle cells. Alpha 2 beta 1 integrin is required for chemotaxis across type I collagen-coated membranes. Am J Pathol 145(5):1070–1081PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  1. 1.Department of Cell Biology and AnatomyLouisiana State University Health Sciences Center – ShreveportShreveportUSA
  2. 2.Department of Cellular and Molecular PhysiologyLouisiana State University Health Sciences Center – ShreveportShreveportUSA
  3. 3.Department of Pathology and Translational PathobiologyLouisiana State University Health Sciences Center – ShreveportShreveportUSA

Personalised recommendations