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Transcription factor and kinase-mediated signaling in atherosclerosis and vascular injury

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Abstract

Our understanding of the molecular signaling pathways regulating the initiation and progression of atherosclerosis or remodeling in response to injury has begun to cross the boundaries from regulation of well-described canonical pathways to the interplay between these pathways. The focus of this review is to summarize our current understanding of a finite group of transcription factors and kinases involved in vascular injury and atherosclerosis, including nuclear factor-κB (NF-κB), early growth response factor-I (Egr-I), activator protein-I (AP-I), hypoxia inducible factor-Iα (HIF-Iα), homeobox, and T cell factor/lymphoid enhancer factor (Tcf-Lef), as well as the kinases janus kinase/signal transducers and activators of transcription (JAK/STAT), protein kinase C (PKC), p38, Rho, ERK5, JNK, p44/p42, and phosphoinositide 3 (PI3) kinase/AKT.

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References and Recommended Reading

  1. Ganesh SK, Skelding KA, Mehta L, et al.: Rationale and study design of the CardioGene Study: genomics of instent restenosis. Pharmacogenomics 2004, 5:952–1004.

    Article  PubMed  Google Scholar 

  2. de Winther MP, Kanters E, Kraal G, Hofker MH: Nuclear factor kappaB signaling in atherogenesis. Arterioscler Thromb Vasc Biol 2005, 25:904–914.

    Article  PubMed  CAS  Google Scholar 

  3. Bolick DT, Orr AW, Whetzel A, et al.: 12/15-lipoxygenase regulates intercellular adhesion molecule-1 expression and monocyte adhesion to endothelium through activation of RhoA and nuclear factor-kappaB. Arterioscler Thromb Vasc Biol 2005, 25:2301–2307.

    Article  PubMed  CAS  Google Scholar 

  4. Lotzer K, Funk CD, Habenicht AJ: The 5-lipoxygenase pathway in arterial wall biology and atherosclerosis. Biochim Biophys Acta 2005, 1736:30–37.

    PubMed  Google Scholar 

  5. Natarajan R, Reddy MA, Malik KU, et al.: Signaling mechanisms of nuclear factor-kappab-mediated activation of inflammatory genes by 13-hydroperoxyoctadecadienoic acid in cultured vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2001, 21:1408–1413.

    PubMed  CAS  Google Scholar 

  6. Brand K, Page S, Rogler G, et al.: Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Invest 1996, 97:1715–1722.

    PubMed  CAS  Google Scholar 

  7. Wilson SH, Best PJ, Edwards WD, et al.: Nuclear factor-kappaB immunoreactivity is present in human coronary plaque and enhanced in patients with unstable angina pectoris. Atherosclerosis 2002, 160:147–153.

    Article  PubMed  CAS  Google Scholar 

  8. Landry DB, Couper LL, Bryant SR, Lindner V: Activation of the NF-kappa B and I kappa B system in smooth muscle cells after rat arterial injury. Induction of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Am J Pathol 1997, 151:1085–1095.

    PubMed  CAS  Google Scholar 

  9. Lindner V: The NF-kappaB and IkappaB system in injured arteries. Pathobiology 1998, 66:311–320.

    Article  PubMed  CAS  Google Scholar 

  10. Rodriguez-Porcel M, Lerman LO, Holmes DR Jr, et al.: Chronic antioxidant supplementation attenuates nuclear factor-kappa B activation and preserves endothelial function in hypercholesterolemic pigs. Cardiovasc Res 2002, 53:1010–1018.

    Article  PubMed  CAS  Google Scholar 

  11. Lin R, Liu J, Peng N, et al.: Lovastatin reduces nuclear factor kappaB activation induced by C-reactive protein in human vascular endothelial cells. Biol Pharm Bull 2005, 28:1630–1634.

    Article  PubMed  CAS  Google Scholar 

  12. Guan Z, Basi D, Li Q, et al.: Loss of redox factor 1 decreases NF-kappaB activity and increases susceptibility of endothelial cells to apoptosis. Arterioscler Thromb Vasc Biol 2005, 25:96–101.

    PubMed  CAS  Google Scholar 

  13. Hall JL, Wang X, Van A, et al.: Overexpression of Ref-1 inhibits hypoxia and tumor necrosis factor-induced endothelial cell apoptosis through nuclear factor-kappaB-independent and -dependent pathways. Circ Res 2001, 88:1247–1253.

    PubMed  CAS  Google Scholar 

  14. Kanters E, Pasparakis M, Gijbels MJ, et al.: Inhibition of NF-kappaB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice. J Clin Invest 2003, 112:1176–1185.

    Article  PubMed  CAS  Google Scholar 

  15. Kanters E, Gijbels MJ, van der Made I, et al.: Hematopoietic NF-kappaB1 deficiency results in small atherosclerotic lesions with an inflammatory phenotype. Blood 2004, 103:934–940.

    Article  PubMed  CAS  Google Scholar 

  16. Jawien J, Gajda M, Mateuszuk L, et al.: Inhibition of nuclear factor-kappaB attenuates artherosclerosis in apoE/LDLR-double knockout mice. J Physiol Pharmacol 2005, 56:483–489.

    PubMed  CAS  Google Scholar 

  17. Lee SH, Schloss DJ, Jarvis L, et al.: Inhibition of angiogenesis by a mouse sprouty protein. J Biol Chem 2001, 276:4128–4133.

    Article  PubMed  CAS  Google Scholar 

  18. Zhu XY, Rodriguez-Porcel M, Bentley MD, et al.: Antioxidant intervention attenuates myocardial neovascularization in hypercholesterolemia. Circulation 2004, 109:2109–2115.

    Article  PubMed  CAS  Google Scholar 

  19. Wilson SH, Herrmann J, Lerman LO, et al.: Simvastatin preserves the structure of coronary adventitial vasa vasorum in experimental hypercholesterolemia independent of lipid lowering. Circulation 2002, 105:415–418.

    Article  PubMed  CAS  Google Scholar 

  20. Fuchs S, Kornowski R, Leon MB, Epstein SE: Anti-angiogenesis: a new potential strategy to inhibit restenosis. Int J Cardiovasc Intervent 2001, 4:3–6.

    Article  PubMed  Google Scholar 

  21. Duckers HJ, Boehm M, True AL, et al.: Heme oxygenase-1 protects against vascular constriction and proliferation. Nat Med 2001, 7:693–698.

    Article  PubMed  CAS  Google Scholar 

  22. Blaschke F, Bruemmer D, Law RE: Egr-1 is a major vascular pathogenic transcription factor in atherosclerosis and restenosis. Rev Endocr Metab Disord 2004, 5:249–254.

    Article  PubMed  CAS  Google Scholar 

  23. Santiago FS, Lowe HC, Day FL, et al.: Early growth response factor-1 induction by injury is triggered by release and paracrine activation by fibroblast growth factor-2. Am J Pathol 1999, 154:937–944.

    PubMed  CAS  Google Scholar 

  24. Silverman ES, Khachigian LM, Santiago FS, et al.: Vascular smooth muscle cells express the transcriptional corepressor NAB2 in response to injury. Am J Pathol 1999, 155:1311–1317.

    PubMed  CAS  Google Scholar 

  25. Silverman ES, Collins T: Pathways of Egr-1-mediated gene transcription in vascular biology. Am J Pathol 1999, 154:665–670.

    PubMed  CAS  Google Scholar 

  26. Du B, Fu C, Kent KC, et al.: Elevated Egr-1 in human atherosclerotic cells transcriptionally represses the transforming growth factor-beta type II receptor. J Biol Chem 2000, 275:39039–39047.

    Article  PubMed  CAS  Google Scholar 

  27. McCaffrey TA, Fu C, Du B, et al.: High-level expression of Egr-1 and Egr-1-inducible genes in mouse and human atherosclerosis. J Clin Invest 2000, 105:653–662.

    Article  PubMed  CAS  Google Scholar 

  28. Fahmy RG, Khachigian LM: Antisense Egr-1 RNA driven by the CMV promoter is an inhibitor of vascular smooth muscle cell proliferation and regrowth after injury. J Cell Biochem 2002, 84:575–582.

    Article  PubMed  CAS  Google Scholar 

  29. Lowe HC, Fahmy RG, Kavurma MM, et al.: Catalytic oligodeoxynucleotides define a key regulatory role for early growth response factor-1 in the porcine model of coronary in-stent restenosis. Circ Res 2001, 89:670–677.

    PubMed  CAS  Google Scholar 

  30. Santiago FS, Atkins DG, Khachigian LM: Vascular smooth muscle cell proliferation and regrowth after mechanical injury in vitro are Egr-1/NGFI-A-dependent. Am J Pathol 1999, 155:897–905.

    PubMed  CAS  Google Scholar 

  31. Santiago FS, Lowe HC, Kavurma MM, et al.: New DNA enzyme targeting Egr-1 mRNA inhibits vascular smooth muscle proliferation and regrowth after injury. Nat Med 1999, 5:1264–1269.

    Article  PubMed  CAS  Google Scholar 

  32. Li C, Xu Q: Mechanical stress-initiated signal transductions in vascular smooth muscle cells. Cell Signal 2000, 12:435–445.

    Article  PubMed  CAS  Google Scholar 

  33. Yasumoto H, Kim S, Zhan Y, et al.: Dominant negative c-jun gene transfer inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia in rats. Gene Ther 2001, 8:1682–1689.

    Article  PubMed  CAS  Google Scholar 

  34. Ahn JD, Morishita R, Kaneda Y, et al.: Inhibitory effects of novel AP-1 decoy oligodeoxynucleotides on vascular smooth muscle cell proliferation in vitro and neointimal formation in vivo. Circ Res 2002, 90:1325–1332.

    Article  PubMed  CAS  Google Scholar 

  35. Gorski DH, Walsh K: Control of vascular cell differentiation by homeobox transcription factors. Trends Cardiovasc Med 2003, 13:213–220.

    Article  PubMed  CAS  Google Scholar 

  36. Bergwerff M, Gittenberger-de Groot AC, Wisse LJ, et al.: Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus. Virchows Arch 2000, 436:12–19.

    Article  PubMed  CAS  Google Scholar 

  37. Chisaka O: Functional analysis of mouse Hox genes by gene targeting. Tanpakushitsu Kakusan Koso 1991, 36:2409–2417.

    PubMed  CAS  Google Scholar 

  38. Kirby ML, Hunt P, Wallis K, Thorogood P: Abnormal patterning of the aortic arch arteries does not evoke cardiac malformations. Dev Dyn 1997, 208:34–47.

    Article  PubMed  CAS  Google Scholar 

  39. Bostrom K, Tintut Y, Kao SC, et al.: HOXB7 overexpression promotes differentiation of C3H10T1/2 cells to smooth muscle cells. J Cell Biochem 2000, 78:210–221.

    Article  PubMed  CAS  Google Scholar 

  40. Perlman H, Luo Z, Krasinski K, et al.: Adenovirus-mediated delivery of the Gax transcription factor to rat carotid arteries inhibits smooth muscle proliferation and induces apoptosis. Gene Ther 1999, 6:758–763.

    Article  PubMed  CAS  Google Scholar 

  41. Smith RC, Branellec D, Gorski DH, et al.: p21CIP1-mediated inhibition of cell proliferation by overexpression of the gax homeodomain gene. Genes Dev 1997, 11:1674–1689.

    PubMed  CAS  Google Scholar 

  42. Fuchs SY, Ougolkov AV, Spiegelman VS, Minamoto T: Oncogenic beta-catenin signaling networks in colorectal cancer. Cell Cycle 2005, 4:1522–1539.

    PubMed  CAS  Google Scholar 

  43. Grant SF, Thorleifsson G, Reynisdottir I, et al.: Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 2006, In press.

  44. Wang X, Adhikari N, Li Q, et al.: The role of [beta]-transducin repeat-containing protein ([beta]-TrCP) in the regulation of NF-[kappa]B in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2004, 24:85–90.

    Article  PubMed  CAS  Google Scholar 

  45. Wang X, Adhikari N, Li Q, Hall JL: LDL receptor-related protein LRP6 regulates proliferation and survival through the Wnt cascade in vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 2004, 287:H2376-H2383.

    Article  PubMed  CAS  Google Scholar 

  46. Wang X, Xiao Y, Mou Y, et al.: A role for the beta-catenin/T-cell factor signaling cascade in vascular remodeling. Circ Res 2002, 90:340–347.

    Article  PubMed  CAS  Google Scholar 

  47. Griendling KK, Ushio-Fukai M, Lassegue B, Alexander RW: Angiotensin II signaling in vascular smooth muscle. New concepts. Hypertension 1997, 29:366–373.

    PubMed  CAS  Google Scholar 

  48. Marrero MB, Schieffer B, Li B, et al.: Role of Janus kinase/signal transducer and activator of transcription and mitogen-activated protein kinase cascades in angiotensin II- and platelet-derived growth factor-induced vascular smooth muscle cell proliferation. J Biol Chem 1997, 272:24684–24690.

    Article  PubMed  CAS  Google Scholar 

  49. Schieffer B, Luchtefeld M, Braun S, et al.: Role of NAD(P)H oxidase in angiotensin II-induced JAK/STAT signaling and cytokine induction. Circ Res 2000, 87:1195–1201.

    PubMed  CAS  Google Scholar 

  50. Tang C, Vaughan AM, Oram JF: Janus kinase 2 modulates the apolipoprotein interactions with ABCA1 required for removing cellular cholesterol. J Biol Chem 2004, 279:7622–7628.

    Article  PubMed  CAS  Google Scholar 

  51. Grote K, Luchtefeld M, Schieffer B: JANUS under stress—role of JAK/STAT signaling pathway in vascular diseases. Vascul Pharmacol 2005, 43:357–363.

    Article  PubMed  CAS  Google Scholar 

  52. Griendling KK, Sorescu D, Lassegue B, Ushio-Fukai M: Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol 2000, 20:2175–2183.

    PubMed  CAS  Google Scholar 

  53. Griendling KK, Ushio-Fukai M: Reactive oxygen species as mediators of angiotensin II signaling. Regul Pept 2000, 91:21–27.

    Article  PubMed  CAS  Google Scholar 

  54. Griendling KK, Ushio-Fukai M: Redox control of vascular smooth muscle proliferation. J Lab Clin Med 1998, 132:9–15.

    Article  PubMed  CAS  Google Scholar 

  55. Schieffer B, Schieffer E, Hilfiker-Kleiner D, et al.: Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability. Circulation 2000, 101:1372–1378.

    PubMed  CAS  Google Scholar 

  56. Kakisis JD, Pradhan S, Cordova A, et al.: The role of STAT-3 in the mediation of smooth muscle cell response to cyclic strain. Int J Biochem Cell Biol 2005, 37:1396–1406.

    Article  PubMed  CAS  Google Scholar 

  57. Chida K, Hara T, Hirai T, et al.: Disruption of protein kinase Ceta results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis. Cancer Res 2003, 63:2404–2408.

    PubMed  CAS  Google Scholar 

  58. Mayr M, Chung YL, Mayr U, et al.: Loss of PKC-delta alters cardiac metabolism. Am J Physiol Heart Circ Physiol 2004, 287:H937-H945.

    Article  PubMed  CAS  Google Scholar 

  59. Andrassy M, Belov D, Harja E, et al.: Central role of PKCbeta in neointimal expansion triggered by acute arterial injury. Circ Res 2005, 96:476–483.

    Article  PubMed  CAS  Google Scholar 

  60. Leitges M, Mayr M, Braun U, et al.: Exacerbated vein graft arteriosclerosis in protein kinase Cdelta-null mice. J Clin Invest 2001, 108:1505–1512.

    Article  PubMed  CAS  Google Scholar 

  61. Ju H, Nerurkar S, Sauermelch CF, et al.: Sustained activation of p38 mitogen-activated protein kinase contributes to the vascular response to injury. J Pharmacol Exp Ther 2002, 301:15–20.

    Article  PubMed  CAS  Google Scholar 

  62. Ohashi N, Matsumori A, Furukawa Y, et al.: Role of p38 mitogen-activated protein kinase in neointimal hyperplasia after vascular injury. Arterioscler Thromb Vasc Biol 2000, 20:2521–2526.

    PubMed  CAS  Google Scholar 

  63. Mudgett JS, Ding J, Guh-Siesel L, et al.: Essential role for p38alpha mitogen-activated protein kinase in placental angiogenesis. Proc Natl Acad Sci U S A 2000, 97:10454–10459.

    Article  PubMed  CAS  Google Scholar 

  64. Beardmore VA, Hinton HJ, Eftychi C, et al.: Generation and characterization of p38beta (MAPK11) gene-targeted mice. Mol Cell Biol 2005, 25:10454–10464.

    Article  PubMed  CAS  Google Scholar 

  65. Seasholtz TM, Brown JH: RHO Signaling in vascular diseases. Mol Interv 2004, 4:348–357.

    Article  PubMed  CAS  Google Scholar 

  66. von Ballmoos MW, Dubler D, Mirlacher M, et al.: Increased apolipoprotein deposits in early atherosclerotic lesions distinguish symptomatic from asymptomatic patients. Arterioscler Thromb Vasc Biol 2005, In press.

  67. Archacki SR, Angheloiu G, Tian XL, et al.: Identification of new genes differentially expressed in coronary artery disease by expression profiling. Physiol Genomics 2003, 15:65–74.

    PubMed  CAS  Google Scholar 

  68. Negoro N, Hoshiga M, Seto M, et al.: The kinase inhibitor fasudil (HA-1077) reduces intimal hyperplasia through inhibiting migration and enhancing cell loss of vascular smooth muscle cells. Biochem Biophys Res Commun 1999, 262:211–215.

    Article  PubMed  CAS  Google Scholar 

  69. Sawada N, Itoh H, Ueyama K, et al.: Inhibition of rho-associated kinase results in suppression of neointimal formation of balloon-injured arteries. Circulation 2000, 101:2030–2033.

    PubMed  CAS  Google Scholar 

  70. Shibata R, Kai H, Seki Y, et al.: Role of Rho-associated kinase in neointima formation after vascular injury. Circulation 2001, 103:284–289.

    PubMed  CAS  Google Scholar 

  71. Matsumoto Y, Uwatoku T, Oi K, et al.: Long-term inhibition of Rho-kinase suppresses neointimal formation after stent implantation in porcine coronary arteries: involvement of multiple mechanisms. Arterioscler Thromb Vasc Biol 2004, 24:181–186.

    Article  PubMed  CAS  Google Scholar 

  72. Miyata K, Shimokawa H, Kandabashi T, et al.: Rho-kinase is involved in macrophage-mediated formation of coronary vascular lesions in pigs in vivo. Arterioscler Thromb Vasc Biol 2000, 20:2351–2358.

    PubMed  CAS  Google Scholar 

  73. Eto Y, Shimokawa H, Hiroki J, et al.: Gene transfer of dominant negative Rho kinase suppresses neointimal formation after balloon injury in pigs. Am J Physiol Heart Circ Physiol 2000, 278:H1744-H1750.

    PubMed  CAS  Google Scholar 

  74. Mallat Z, Gojova A, Sauzeau V, et al.: Rho-associated protein kinase contributes to early atherosclerotic lesion formation in mice. Circ Res 2003, 93:884–888.

    Article  PubMed  CAS  Google Scholar 

  75. Kataoka C, Egashira K, Inoue S, et al.: Important role of Rhokinase in the pathogenesis of cardiovascular inflammation and remodeling induced by long-term blockade of nitric oxide synthesis in rats. Hypertension 2002, 39:245–250.

    Article  PubMed  CAS  Google Scholar 

  76. Herdeg C, Fitzke M, Oberhoff M, et al.: Effects of atorvastatin on in-stent stenosis in normo- and hypercholesterolemic rabbits. Int J Cardiol 2003, 91:59–69.

    Article  PubMed  Google Scholar 

  77. Ni W, Egashira K, Kataoka C, et al.: Antiinflammatory and antiarteriosclerotic actions of HMG-CoA reductase inhibitors in a rat model of chronic inhibition of nitric oxide synthesis. Circ Res 2001, 89:415–421.

    PubMed  CAS  Google Scholar 

  78. Hayashi M, Lee JD: Role of the BMK1/ERK5 signaling pathway: lessons from knockout mice. J Mol Med 2004, 82:800–808.

    Article  PubMed  CAS  Google Scholar 

  79. Abe J, Kusuhara M, Ulevitch RJ, et al.: Big mitogenactivated protein kinase 1 (BMK1) is a redox-sensitive kinase. J Biol Chem 1996, 271:16586–16590.

    Article  PubMed  CAS  Google Scholar 

  80. Regan CP, Li W, Boucher DM, et al.: Erk5 null mice display multiple extraembryonic vascular and embryonic cardiovascular defects. Proc Natl Acad Sci U S A 2002, 99:9248–9253.

    Article  PubMed  CAS  Google Scholar 

  81. Yang J, Boerm M, McCarty M, et al.: Mekk3 is essential for early embryonic cardiovascular development. Nat Genet 2000, 24:309–313.

    Article  PubMed  CAS  Google Scholar 

  82. Pi X, Garin G, Xie L, et al.: BMK1/ERK5 is a novel regulator of angiogenesis by destabilizing hypoxia inducible factor 1alpha. Circ Res 2005, 96:1145–1151.

    Article  PubMed  CAS  Google Scholar 

  83. Yan C, Luo H, Lee JD, et al.: Molecular cloning of mouse ERK5/BMK1 splice variants and characterization of ERK5 functional domains. J Biol Chem 2001, 276:10870–10878.

    Article  PubMed  CAS  Google Scholar 

  84. Hayashi M, Kim SW, Imanaka-Yoshida K, et al.: Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure. J Clin Invest 2004, 113:1138–1148.

    Article  PubMed  CAS  Google Scholar 

  85. Lin Q, Schwarz J, Bucana C, Olson EN: Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. Science 1997, 276:1404–1407.

    Article  PubMed  CAS  Google Scholar 

  86. Sumara G, Belwal M, Ricci R: “Jnking” atherosclerosis. Cell Mol Life Sci 2005, 62:2487–2494.

    Article  PubMed  CAS  Google Scholar 

  87. Kuan CY, Yang DD, Samanta Roy DR, et al.: The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron 1999, 22:667–676.

    Article  PubMed  CAS  Google Scholar 

  88. Sabapathy K, Jochum W, Hochedlinger K, et al.: Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2. Mech Dev 1999, 89:115–124.

    Article  PubMed  CAS  Google Scholar 

  89. Ricci R, Sumara G, Sumara I, et al.: Requirement of JNK2 for scavenger receptor A-mediated foam cell formation in atherogenesis. Science 2004, 306:1558–1561.

    Article  PubMed  CAS  Google Scholar 

  90. Pages G, Guerin S, Grall D, et al.: Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice. Science 1999, 286:1374–1377.

    Article  PubMed  CAS  Google Scholar 

  91. Kuida K, Boucher DM: Functions of MAP kinases: insights from gene-targeting studies. J Biochem (Tokyo) 2004, 135:653–656.

    CAS  Google Scholar 

  92. Senokuchi T, Matsumura T, Sakai M, et al.: Extracellular signal-regulated kinase and p38 mitogen-activated protein kinase mediate macrophage proliferation induced by oxidized low-density lipoprotein. Atherosclerosis 2004, 176:233–245.

    Article  PubMed  CAS  Google Scholar 

  93. Dumitru CD, Ceci JD, Tsatsanis C, et al.: TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell 2000, 103:1071–1083.

    Article  PubMed  CAS  Google Scholar 

  94. Eliopoulos AG, Dumitru CD, Wang CC, et al.: Induction of COX-2 by LPS in macrophages is regulated by Tpl2-dependent CREB activation signals. EMBO J 2002, 21:4831–4840.

    Article  PubMed  CAS  Google Scholar 

  95. Eliopoulos AG, Wang CC, Dumitru CD, Tsichlis PN: Tpl2 transduces CD40 and TNF signals that activate ERK and regulates IgE induction by CD40. EMBO J 2003, 22:3855–3864.

    Article  PubMed  CAS  Google Scholar 

  96. Chan TO, Rittenhouse SE, Tsichlis PN: AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem 1999, 68:965–1014.

    Article  PubMed  CAS  Google Scholar 

  97. Brodbeck D, Cron P, Hemmings BA: A human protein kinase Bgamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain. J Biol Chem 1999, 274:9133–9136.

    Article  PubMed  CAS  Google Scholar 

  98. Brodbeck D, Hill MM, Hemmings BA: Two splice variants of protein kinase B gamma have different regulatory capacity depending on the presence or absence of the regulatory phosphorylation site serine 472 in the carboxyl-terminal hydrophobic domain. J Biol Chem 2001, 276:29550–29558.

    Article  PubMed  CAS  Google Scholar 

  99. Walter DH, Dimmeler S, Zeiher AM: Effects of statins on endothelium and endothelial progenitor cell recruitment. Semin Vasc Med 2004, 4:385–393.

    Article  PubMed  Google Scholar 

  100. Walter DH, Zeiher AM, Dimmeler S: Effects of statins on endothelium and their contribution to neovascularization by mobilization of endothelial progenitor cells. Coronary Artery Dis 2004, 15:235–242.

    Article  Google Scholar 

  101. Chen WS, Xu PZ, Gottlob K, et al.: Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev 2001, 15:2203–2208.

    Article  PubMed  CAS  Google Scholar 

  102. Cho H, Mu J, Kim JK, et al.: Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science 2001, 292:1728–1731.

    Article  PubMed  CAS  Google Scholar 

  103. Daly C, Wong V, Burova E, et al.: Angiopoietin-1 modulates endothelial cell function and gene expression via the transcription factor FKHR (FOXO1). Genes Dev 2004, 18:1060–1071.

    Article  PubMed  CAS  Google Scholar 

  104. Park KW, Kim DH, You HJ, et al.: Activated forkhead transcription factor inhibits neointimal hyperplasia after angioplasty through induction of p27. Arterioscler Thromb Vasc Biol 2005, 25:742–747.

    Article  PubMed  CAS  Google Scholar 

  105. Greer EL, Brunet A: FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 2005, 24:7410–7425.

    Article  PubMed  CAS  Google Scholar 

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  1. Cardiovascular Division, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 508, 55455, Minneapolis, MN, USA

    Jennifer L. Hall PhD

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  1. Neeta Adhikari PhD
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Adhikari, N., Charles, N., Lehmann, U. et al. Transcription factor and kinase-mediated signaling in atherosclerosis and vascular injury. Curr Atheroscler Rep 8, 252–260 (2006). https://doi.org/10.1007/s11883-006-0081-1

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