• 1
    Plump AS, Smith JD, Hayek T et al. Hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 1992; 71: 343353.
  • 2
    Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb 1994; 14: 133140.
  • 3
    Ross R. Atherosclerosis – An inflammatory disease. N Engl J Med 1999; 340: 115126.
  • 4
    Jonasson L, Holm J, Skalli O, Bondjers G, Hansson GK. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis 1986; 6: 131138.
  • 5
    Hansson GK, Jonasson L, Lojsthed B, Stemme S, Kocher O, Gabbiani G. Localization of T lymphocytes and macrophages in fibrous and complicated human atherosclerotic plaques. Atherosclerosis 1988; 72: 135141.
  • 6
    Hansson GK, Holm J, Jonasson L. Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol 1989; 135: 169175.
  • 7
    Kishikawa H, Shimokama T, Watanabe T. Localization of T lymphocytes and macrophages expressing IL-1, IL-2 receptor, IL-6 and TNF in human aortic intima. Role of cell-mediated immunity in human atherogenesis. Virchows Archiv A Pathol Anat 1993; 423: 433442.
  • 8
    Rekhter MD, Gordon D. Active proliferation of different cell types, including lymphocytes, in human atherosclerotic plaques. Am J Pathol 1995; 147: 668677.
  • 9
    Sehgal SN, Molnar-Kimber K, Ocain TD, Weichman BM. Rapamycin: a novel immunosuppressive macrolide. Med Res Rev 1994; 14: 122.
  • 10
    Cardenas ME, Zhu D, Heitman J. Molecular mechanisms of immunosuppression by cyclosporine, FK506, and rapamycin. Curr Opin Nephrol Hyperten 1995; 4: 472477.
  • 11
    Heitman J, Movva NR, Hall MN. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 1991; 253: 905909.
  • 12
    Luo Y, Marx SO, Kiyokawa H, Koff A, Massague J, Marks AR. Rapamycin resistance tied to defective regulation of p27Kip1. Mol Cell Biol 1996; 16: 67446751.
  • 13
    Nakayama K, Ishida N, Shirane M et al. Mice lacking p27 (Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 1996; 85: 707720.
  • 14
    Emeson EE, Shen M-L. Accelerated atherosclerosis in hyperlipidemic C57BL/6 mice treated with cyclosporin A. Am J Pathol 1993; 142: 19061915.
  • 15
    Roselaar SE, Schonfeld G, Daugherty A. Enhanced development of atherosclerosis in cholesterol-fed rabbits by suppression of cell-mediated immunity. J Clin Invest 1995; 96: 13891394.
  • 16
    Drew AF, Tipping PG. Cyclosporine treatment reduces early atherosclerosis in the cholesterol-fed rabbit. Atherosclerosis 1995; 116: 181189.
  • 17
    Paigen B, Morrow A, Holmes PA, Mitchell D, Williams RA. Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 1987; 68: 231240.
  • 18
    Uyemura K, Demer LL, Castle SC et al. Cross-regulatory roles of interleukin (IL) -12 and IL-10 in atherosclerosis. J Clin Invest 1996; 97: 21302138.
  • 19
    Gupta S, Pablo AM, Jiang X-C, Wang N, Tall AR, Schindler C. IFN-γ potentiates atherosclerosis in apoE knock-out mice. J Clin Invest 1997; 99: 27522761.
  • 20
    Lee T-S, Yen H-C, Pan C-C, Chau L-Y. The role of interleukin 12 in the development of atherosclerosis in apoE-deficient mice. Arterioscler Thromb Vasc Biol 1999; 19: 734742.
  • 21
    Pinderski Oslund LJ, Hedrick CC, Olvera T et al. Interleukin-10 blocks atherosclerotic events in vitro and in vivo. Arterioscler Thromb Vasc Biol 1999; 19: 28472853.
  • 22
    Mallat Z, Heymes C, Ohan J, Faggin E, Leseche G, Tedgui A. Expression of interleukin-10 in advanced human atherosclerotic plaques. Relation to inducible nitric oxide synthase expression and cell death. Arterioscler Thromb Vasc Biol 1999; 19: 611616.
  • 23
    Huber SA, Sakkinen P, David C, Newell MK, Tracy RP. T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia. Circulation 2001; 103: 26102616.
  • 24
    Heimark RL, Twardzik DR, Schwartz SM. Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets. Science 1986; 233: 10781080.
  • 25
    Assoian RK, Sporn MB. Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol 1986; 102: 12171223.
  • 26
    Letterio JJ, Roberts AB. Regulation of immune responses by TGF-β. Annu Rev Immunol 1998; 16: 137161.
  • 27
    Fyfe AI, Qiao J-H, Lusis AJ. Immune-deficient mice develop typical atherosclerotic fatty streaks when fed and atherogenic diet. J Clin Invest 1994; 94: 25162520.
  • 28
    Emeson EE, Shen M-L, Bell CGH, Qureshi A. Inhibition of atherosclerosis in CD4 T-cell-ablated and nude (nu/nu) C57BL/6 hyperlipidemic mice. Am J Pathol 1996; 149: 675685.
  • 29
    Daugherty A, Pure E, Delfel-Butteiger D, Chen S, Leferovich J, Roselaar SE. The effects of total lymphocyte deficiency on the extent of atherosclerosis in apolipoprotein E-/- mice. J Clin Invest 1997; 100: 15751580.
  • 30
    Dansky HM, Charlton SA, Harper MM, Smith JD. T and B lymphocytes play a minor role in atherosclerotic plaque formation in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci 1997; 94: 46424646.
  • 31
    Song L, Leung C, Schindler C. Lymphocytes are important in early atherosclerosis. J Clin Invest 2001; 108: 251259.
  • 32
    Reardon CA, Blachowicz L, White T et al. Effect of immune deficiency on lipoproteins and atherosclerosis in male apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2001; 21: 10111016.
  • 33
    Zhou X, Nicoletti A, Elhage R, Hansson GK. Transfer of CD4+ T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice. Circulation 2000; 102: 29192922.
  • 34
    Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7: 145173.
  • 35
    Laurat E, Poirier B, Tupin E et al. In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis in apolipoprotein E-knockout mice. Circulation 2001; 104: 197202.
  • 36
    Dodge IL, Demirci G, Strom TB, Li XC. Rapamycin induces transforming growth factor-β production by lymphocytes. Transplantation 2000; 70: 11041106.
  • 37
    Khanna AK. Mechanism of the combination immunosuppressive effects of rapamycin with either cyclosporine or tacrolimus. Transplantation 2000; 70: 690694.
  • 38
    Wasowska BA, Zheng XX, Strom TB, Kupiec-Weglinski JW. Adjunctive rapamycin and CsA treatment inhibits monocyte/macrophage associated cytokines/chemokines in sensitized cardiac graft recipients. Transplantation 2001; 71: 11791183.
  • 39
    Khanna A, Li B, Stenzel KH, Suthanthiran M. Regulation of new DNA synthesis in mammalian cells by cyclosporine. Transplantation 1994; 57: 577582.
  • 40
    Prashar Y, Khanna A, Sehajpal P, Sharma VK, Suthanthiran M. Stimulation of transforming growth factor-β1 by cyclosporine. FEBS Lett 1995; 358: 109112.
  • 41
    Ahuja SS, Shrivastav S, Danielpour D, Balow JE, Boumpas DT. Regulation of transforming growth factor-beta 1 and its receptor by cyclosporine in human T lymphocytes. Transplantation 1995; 60: 718723.
  • 42
    Wolf G, Thaiss F, Stahl RA. Cyclosporine stimulates expression of transforming growth factor-beta in renal cells. Possible mechanism of cyclosporines antiprolliferative effects. Transplantation 1995; 60: 237241.
  • 43
    Khanna A, Kapur S, Sharma V, Li B, Suthanthiran M. In vivo hyperexpression of transforming growth factor-β1 in mice: stimulation by cyclosporine. Transplantation 1997; 63: 10371039.
  • 44
    Shin G-T, Khanna A, Ding R et al. In vivo expression of transforming growth factor-b1 in humans. Transplantation 1998; 65: 313318.
  • 45
    Khanna AK, Cairns VR, Becker CG, Hosenpud JD. Transforming growth factor (TGF) -β mimics and anti-TGF-β antibody abrogates the in vivo effects of cyclosporine. Transplantation 1999; 67: 882889.
  • 46
    Majesky MW, Lindner V, Twardzik DR, Schwartz SM, Reidy MA. Production of transforming growth factor β1 during repair of arterial injury. J Clin Invest 1991; 88: 904910.
  • 47
    Nikol S, Isner JM, Kearney M, Leclerc G, Weir L. Expression of transforming growth factor-β1 is increased in human vascular restenosis lesions. J Clin Invest 1992; 90: 15821592.
  • 48
    Wolf YG, Rasmussen LM, Ruoslahti E. Antibodies against transforming growth factor-β1 suppress intimal hyperplasia in a rat model. J Clin Invest 1994; 93: 11721178.
  • 49
    Nabel EG, Shum L, Pompili VJ et al. Direct transfer of transforming growth factor β1 gene into arteries stimulates fibrocellular hyperplasia. Proc Natl Acad Sci 1993; 90: 1075910763.
  • 50
    Schulick AH, Taylor AJ, Zuo W et al. Overexpression of transforming growth factor β1 in arterial endothelium causes hyperplasia, apoptosis, and cartilaginous metaplasia. Proc Natl Acad Sci 1998; 95: 69836988.
  • 51
    Owens GK, Geisterfer AT, Yang YW-HA, Komoriya A. Transforming growth factor-β-induced growth inhibition and cellular hypertrophy in cultured vascular smooth muscle cells. J Cell Biol 1988; 107: 771780.
  • 52
    Grainger DJ, Kirschenlohr HL, Metcalfe JC, Weissberg PL, Wade DP, Lawn RM. Proliferation of human smooth muscle cells promoted by lipoprotein (a). Science 1993; 260: 16551658.
  • 53
    Grainger DJ, Kemp PR, Liu AC, Lawn RM, Metcalfe JC. Activation of transforming growth factor-β is inhibited in transgenic apolipoprotein (a) mice. Nature 1994; 370: 460462.
  • 54
    Grainger DJ, Metcalfe JC. A pivotal role for TGF-β in atherogenesis? Biol Rev 1995; 70: 571596.
  • 55
    Grainger DJ, Kemp PR, Metcalfe JC et al. The serum concentration of active transforming growth factor-β is severly depressed in advanced atherosclerosis. Nature Med 1995; 1: 7479.
  • 56
    Grainger DJ, Mosedale DE, Metcalfe JC, Bottinger EP. Dietary fat and reduced levels of TGFβ1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions. J Cell Sci 2000; 113: 23552361.
  • 57
    Marx SO, Jayaraman T, Go LO, Marks A. Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells. Circ Res 1995; 76: 412417.
  • 58
    Morris RE, Cao W, Huang X et al. Rapamycin (Sirolimus) inhibits vascular smooth muscle DNA synthesis in vitro and suppresses narrowing in arterial allografts and in balloon-injured carotid arteries: evidence that rapamycin antagonizes growth factor action on immune and nonimmune cells. Transplant Proc 1995; 27: 430431.
  • 59
    Plump A, Scott CJ, Breslow JL. Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci 1994; 91: 96079611.
  • 60
    Gregory CR, Huie P, Billingham ME, Morris RE. Rapamycin inhibits arterial intimal thickening caused by both alloimmune and mechanical injury. Transplantation 1993; 55: 14091418.
  • 61
    Gallo R, Padurean A, Jayaraman T et al. Inhibition of intimal thickening after balloon angioplasty in porcine coronary arteries by targeting regulators of the cell cycle. Circulation 1999; 99: 21642170.
  • 62
    Sousa JE, Costa MA, Abizaid A et al. Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries. A quantitative coronary angiography and three-dimensional intravascular ultrasound study. Circulation 2001; 103: 192195.
  • 63
    Meiser BM, Billingham ME, Morris RE. Effects of cyclosporin, FK506, and rapamycin on graft-vessel disease. Lancet 1991; 338: 12971298.
  • 64
    Ikonen TS, Gummert JF, Hayase M et al. Sirolimus (Rapamycin) halts and reverses progression of allograft vascular disease in non-human primates. Transplantation 2000; 70: 969975.
  • 65
    Mancini D, Pinney S, Burkoff D et al. Use of rapamycin slows progression of cardiac transplant vasculopathy. Circulation 2001; 104 (Suppl. II:): II-714.
  • 66
    Billingham ME. Cardiac transplant atherosclerosis. Transplant Proc 1987; 19: 1925.
  • 67
    Billingham ME. Graft coronary disease: the lesions and the patients. Transplant Proc 1989; 21: 36653666.