Download PDF
Thromb Haemost 2002; 88(04): 554-567
DOI: 10.1055/s-0037-1613256
Review Article
Schattauer GmbH

Cytokines in the Pathogenesis of Atherosclerosis

James L. Young
1   Leducq Center for Cardiovascular Research, Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
,
Peter Libby
1   Leducq Center for Cardiovascular Research, Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
,
Uwe Schönbeck
1   Leducq Center for Cardiovascular Research, Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
› Author AffiliationsThis work was supported by the Fondation Leducq and a MERIT Award to Dr. Peter Libby (NIH/NHLBI, HL34636).
Further Information

Publication History

Received 06 May 2002

Accepted after revision 24 June 2002

Publication Date:
09 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Research during the last two decades established atheromatous lesions as active sites of inflammation and immune responses, contrasting to the traditional view of atherosclerosis as an acellular lesion composed of lipid deposits. In particular, cytokines appear to orchestrate the chronic development of atherosclerosis, eventually leading to the formation of complex atherosclerotic plaques, which can trigger acute thromboembolic complications, such as myocardial infarction or stroke. Indeed the rupture-prone plaque, characterized by a thin fibrous cap overlaying a voluminous lipid core, exhibits accumulation of various pro-inflammatory cytokines. These cytokines may control the clinical consequences of plaques by mediating infiltration and accumulation of immunocompetent cells, directing the turnover of fibrillar collagens (governing the fragility of the fibrous cap), or enhancing foam cell formation and thrombogenicity of the lipid core, among other processes outlined in this review. Thus, understanding the role of cytokines in the pathophysiology of the atherosclerotic plaque might provide a promising therapeutic avenue for this prevalent human disease. This review will focus on members of the interleukin, tumor necrosis factor, and interferon families of cytokines in modulating key processes of atherogenesis.

Keywords

Atherosclerosis - inflammation - interleukin - tumor necrosis factor - interferon
 

  • References

  • 1 2000 Heart and Stroke Statistical Update. Dallas, Tex: American Heart Association; 1999
  • 2 Murray CJL, Lopez AD. The Global Burden of Disease. A comprehensive asessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020 1996.
    PubMedGoogle Scholar
  • 3 Lopez AD, Murray CC. The global burden of disease, 1990-2020. Nat Med 1998; 04 (11) 1241-3.
    CrossrefPubMedGoogle Scholar
  • 4 Alderman EL, Corley SD, Fisher LD, Chaitman BR, Faxon DP, Foster ED. et al. Five-year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). CASS Participating Investigators and Staff. J Am Coll Cardiol 1993; 22 (04) 1141-54.
    CrossrefPubMedGoogle Scholar
  • 5 Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M. et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 1988; 12 (01) 56-62.
    CrossrefPubMedGoogle Scholar
  • 6 Giroud D, Li JM, Urban P, Meier B, Rutishauer W. Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography. Am J Cardiol 1992; 69 (08) 729-32.
    CrossrefPubMedGoogle Scholar
  • 7 Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR. et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease?. Circulation 1988; 78 5 Pt 1 1157-66.
    CrossrefPubMedGoogle Scholar
  • 8 Leibowitz J. The History of Coronary Heart Disease. Berkeley: University of California Press; 1970
    Google Scholar
  • 9 Palmer H, Libby P. Interferon-beta. A potential autocrine regulator of human vascular smooth muscle cell growth. Lab Invest 1992; 66 (06) 715-21.
    PubMedGoogle Scholar
  • 10 Gupta S, Pablo AM, Jiang X, Wang N, Tall AR, Schindler C. IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest 1997; 99 (11) 2752-61.
    CrossrefPubMedGoogle Scholar
  • 11 Micallef MJ, Ohtsuki T, Kohno K, Tanabe F, Ushio S, Namba M. et al. Interferon-gamma-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-gamma production. Eur J Immunol 1996; 26 (07) 1647-51.
    CrossrefPubMedGoogle Scholar
  • 12 Dinarello CA. IL-18: A TH1-inducing, proinflammatory cytokine and new member of the IL-1 family. J Allergy Clin Immunol 1999; 103 1 Pt 1 11-24.
    CrossrefPubMedGoogle Scholar
  • 13 Avice MN, Demeure CE, Delespesse G, Rubio M, Armant M, Sarfati M. IL-15 promotes IL-12 production by human monocytes via T cell-dependent contact and may contribute to IL-12-mediated IFN-gamma secretion by CD4+ T cells in the absence of TCR ligation. J Immunol 1998; 161 (07) 3408-15.
    PubMedGoogle Scholar
  • 14 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 USA 1997; 94 (09) 4642-6.
    CrossrefPubMedGoogle Scholar
  • 15 Zhou X, Nicoletti A, Elhage R, Hansson GK. Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice. Circulation 2000; 102 (24) 2919-22.
    CrossrefPubMedGoogle Scholar
  • 16 Frostegard J, Ulfgren AK, Nyberg P, Hedin U, Swedenborg J, Andersson U. et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis 1999; 145 (01) 33-43.
    CrossrefPubMedGoogle Scholar
  • 17 Ushio S, Namba M, Okura T, Hattori K, Nukada Y, Akita K. et al. Cloning of the cDNA for human IFN-gamma-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein. J Immunol 1996; 156 (11) 4274-9.
    PubMedGoogle Scholar
  • 18 Gerdes N, Sukhova GK, Libby P, Reynolds RS, Young JL, Schonbeck U. Expression of Interleukin (IL)-18 and Functional IL-18 Receptor on Human Vascular Endothelial Cells, Smooth Muscle Cells, and Macrophages: Implications for Atherogenesis. J Exp Med 2002; 195 (02) 245-57.
    CrossrefPubMedGoogle Scholar
  • 19 Mallat Z, Corbaz A, Scoazec A, Besnard S, Leseche G, Chvatchko Y. et al. Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation 2001; 104 (14) 1598-603.
    CrossrefPubMedGoogle Scholar
  • 20 Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med 1999; 340 (02) 115-26.
    CrossrefPubMedGoogle Scholar
  • 21 O’Brien KD, Allen MD, McDonald TO, Chait A, Harlan JM, Fishbein D. et al. Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis. J Clin Invest 1993; 92 (02) 945-51.
    CrossrefPubMedGoogle Scholar
  • 22 Cybulsky MI, Gimbrone Jr MA. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 1991; 251 4995 788-91.
    CrossrefPubMedGoogle Scholar
  • 23 Vora DK, Fang ZT, Liva SM, Tyner TR, Parhami F, Watson AD. et al. Induction of P-selectin by oxidized lipoproteins. Separate effects on synthesis and surface expression. Circ Res 1997; 80 (06) 810-8.
    CrossrefPubMedGoogle Scholar
  • 24 Printseva O, Peclo MM, Gown AM. Various cell types in human atherosclerotic lesions express ICAM-1. Further immunocytochemical and immunochemical studies employing monoclonal antibody 10F3. Am J Pathol 1992; 140 (04) 889-96.
    PubMedGoogle Scholar
  • 25 Norman KE, Moore KL, McEver RP, Ley K. Leukocyte rolling in vivo is mediated by P-selectin glycoprotein ligand-1. Blood 1995; 86 (12) 4417-21.
    PubMedGoogle Scholar
  • 26 Davies MJ, Gordon JL, Gearing AJ, Pigott R, Woolf N, Katz D. et al. The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-electin in human atherosclerosis. J Pathol 1993; 171 (03) 223-9.
    CrossrefPubMedGoogle Scholar
  • 27 Duplaa C, Couffinhal T, Labat L, Moreau C, Petit-Jean ME, Doutre MS. et al. Monocyte/macrophage recruitment and expression of endothelial adhesion proteins in human atherosclerotic lesions. Atherosclerosis 1996; 121 (02) 253-66.
    CrossrefPubMedGoogle Scholar
  • 28 Endres M, Laufs U, Merz H, Kaps M. Focal expression of intercellular adhesion molecule-1 in the human carotid bifurcation. Stroke 1997; 28 (01) 77-82.
    CrossrefPubMedGoogle Scholar
  • 29 Lorant DE, McEver RP, McIntyre TM, Moore KL, Prescott SM, Zimmerman GA. Activation of polymorphonuclear leukocytes reduces their adhesion to P-selectin and causes redistribution of ligands for P-selectin on their surfaces. J Clin Invest 1995; 96 (01) 171-82.
    CrossrefPubMedGoogle Scholar
  • 30 Li H, Cybulsky MI, Gimbrone Jr MA, Libby P. Inducible expression of vascular cell adhesion molecule-1 by vascular smooth muscle cells in vitro and within rabbit atheroma. Am J Pathol 1993; 143 (06) 1551-9.
    PubMedGoogle Scholar
  • 31 Li H, Cybulsky MI, Gimbrone Jr MA, Libby P. An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscler Thromb 1993; 13 (02) 197-204.
    CrossrefPubMedGoogle Scholar
  • 32 Iiyama K, Hajra L, Iiyama M, Li H, DiChiara M, Medoff BD. et al. Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ Res 1999; 85 (02) 199-207.
    CrossrefPubMedGoogle Scholar
  • 33 Nakashima Y, Raines EW, Plump AS, Breslow JL, Ross R. Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. Arterioscler Thromb Vasc Biol 1998; 18 (05) 842-51.
    CrossrefPubMedGoogle Scholar
  • 34 Munro JM. Endothelial-leukocyte adhesive interactions in inflammatory diseases. Eur Heart J 1993; 14 Suppl K 72-7.
    PubMedGoogle Scholar
  • 35 Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, Iiyama M. et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest 2001; 107 (10) 1255-62.
    CrossrefPubMedGoogle Scholar
  • 36 Dong ZM, Chapman SM, Brown AA, Frenette PS, Hynes RO, Wagner DD. The combined role of P-and E-selectins in atherosclerosis. J Clin Invest 1998; 102 (01) 145-52.
    CrossrefPubMedGoogle Scholar
  • 37 Vidal-Vanaclocha F, Fantuzzi G, Mendoza L, Fuentes AM, Anasagasti MJ, Martin J. et al. IL-18 regulates IL-1beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. Proc Natl Acad Sci USA 2000; 97 (02) 734-9.
    CrossrefPubMedGoogle Scholar
  • 38 Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G. et al. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 1989; 59 (06) 1203-11.
    CrossrefPubMedGoogle Scholar
  • 39 Pober JS. Effects of tumour necrosis factor and related cytokines on vascular endothelial cells. Ciba Found Symp 1987; 131: 170-84.
    PubMedGoogle Scholar
  • 40 Myers CL, Wertheimer SJ, Schembri-King J, Parks T, Wallace RW. Induction of ICAM-1 by TNF-alpha, IL-1 beta, and LPS in human endothelial cells after downregulation of PKC. Am J Physiol 1992; 263 4 Pt 1 C767-72.
    CrossrefPubMedGoogle Scholar
  • 41 Briscoe DM, Cotran RS, Pober JS. Effects of tumor necrosis factor, lipopolysaccharide, and IL-4 on the expression of vascular cell adhesion molecule-1 in vivo. Correlation with CD3+ T cell infiltration. J Immunol 1992; 149 (09) 2954-60.
    PubMedGoogle Scholar
  • 42 Szekanecz Z, Shah MR, Pearce WH, Koch AE. Intercellular adhesion molecule-1 (ICAM-1) expression and soluble ICAM-1 (sICAM-1) production by cytokine-activated human aortic endothelial cells: a possible role for ICAM-1 and sICAM-1 in atherosclerotic aortic aneurysms. Clin Exp Immunol 1994; 98 (02) 337-43.
    PubMedGoogle Scholar
  • 43 Hubbard AK, Rothlein R. Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades. Free Radic Biol Med 2000; 28 (09) 1379-86.
    CrossrefPubMedGoogle Scholar
  • 44 Hollenbaugh D, Mischel-Petty N, Edwards CP, Simon JC, Denfeld RW, Kiener PA. et al. Expression of functional CD40 by vascular endothelial cells. J Exp Med 1995; 182 (01) 33-40.
    CrossrefPubMedGoogle Scholar
  • 45 Karmann K, Hughes CC, Schechner J, Fanslow WC, Pober JS. CD40 on human endothelial cells: inducibility by cytokines and functional regulation of adhesion molecule expression. Proc Natl Acad Sci USA 1995; 92 (10) 4342-6.
    CrossrefPubMedGoogle Scholar
  • 46 Yellin MJ, Brett J, Baum D, Matsushima A, Szabolcs M, Stern D. et al. Functional interactions of T cells with endothelial cells: the role of CD40L-CD40-mediated signals. J Exp Med 1995; 182 (06) 1857-64.
    CrossrefPubMedGoogle Scholar
  • 47 Mach F, Schonbeck U, Libby P. CD40 signaling in vascular cells: a key role in atherosclerosis?. Atherosclerosis 1998; 137 Suppl S89-95.
    CrossrefPubMedGoogle Scholar
  • 48 Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature 1998; 394 6689 200-3.
    CrossrefPubMedGoogle Scholar
  • 49 Mach F, Schonbeck U, Sukhova GK, Bourcier T, Bonnefoy JY, Pober JS. et al. Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for CD40-CD40 ligand signaling in atherosclerosis. Proc Natl Acad Sci USA 1997; 94 (05) 1931-6.
    CrossrefPubMedGoogle Scholar
  • 50 Thornhill MH, Haskard DO. IL-4 regulates endothelial cell activation by IL-1, tumor necrosis factor, or IFN-gamma. J Immunol 1990; 145 (03) 865-72.
    PubMedGoogle Scholar
  • 51 Chatelain R, Wollenberg A, Martin C, Panhans-Gross A, Bieber T, Degitz K. et al. IL-10 inhibits ICAM-1 expression on human Langerhans cells but not on keratinocytes, dermal endothelial cells or fibroblasts. Arch Dermatol Res 1998; 290 (09) 477-82.
    CrossrefPubMedGoogle Scholar
  • 52 Couffinhal T, Duplaa C, Moreau C, Lamaziere JM, Bonnet J. Regulation of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in human vascular smooth muscle cells. Circ Res 1994; 74 (02) 225-34.
    CrossrefPubMedGoogle Scholar
  • 53 Navab M, Imes SS, Hama SY, Hough GP, Ross LA, Bork RW. et al. Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. J Clin Invest 1991; 88 (06) 2039-46.
    CrossrefPubMedGoogle Scholar
  • 54 Gu L, Okada Y, Clinton SK, Gerard C, Sukhova GK, Libby P. et al. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 1998; 02 (02) 275-81.
    CrossrefPubMedGoogle Scholar
  • 55 Gerszten RE, Garcia-Zepeda EA, Lim YC, Yoshida M, Ding HA, Gimbrone Jr MA. et al. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 1999; 398 6729 718-23.
    CrossrefPubMedGoogle Scholar
  • 56 Boisvert WA, Santiago R, Curtiss LK, Terkeltaub RA. A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest 1998; 101 (02) 353-63.
    CrossrefPubMedGoogle Scholar
  • 57 Simonini A, Moscucci M, Muller DW, Bates ER, Pagani FD, Burdick MD. et al. IL-8 is an angiogenic factor in human coronary atherectomy tissue. Circulation 2000; 101 (13) 1519-26.
    CrossrefPubMedGoogle Scholar
  • 58 Angiolillo AL, Kanegane H, Sgadari C, Reaman GH, Tosato G. Interleukin-15 promotes angiogenesis in vivo. Biochem Biophys Res Commun 1997; 233 (01) 231-7.
    CrossrefPubMedGoogle Scholar
  • 59 Van Der Meeren A, Squiban C, Gourmelon P, Lafont H, Gaugler MH. Differential regulation by IL-4 and IL-10 of radiation-induced IL-6 and IL-8 production and ICAM-1 expression by human endothelial cells. Cytokine 1999; 11 (11) 831-8.
    CrossrefPubMedGoogle Scholar
  • 60 Geng YJ, Hansson GK. Interferon-gamma inhibits scavenger receptor expression and foam cell formation in human monocyte-derived macrophages. J Clin Invest 1992; 89 (04) 1322-30.
    CrossrefPubMedGoogle Scholar
  • 61 van Lenten BJ, Fogelman AM. Lipopolysaccharide-induced inhibition of scavenger receptor expression in human monocyte-macrophages is mediated through tumor necrosis factor-alpha. J Immunol 1992; 148 (01) 112-6.
    PubMedGoogle Scholar
  • 62 Hsu HY, Nicholson AC, Hajjar DP. Inhibition of macrophage scavenger receptor activity by tumor necrosis factor-alpha is transcriptionally and post-transcriptionally regulated. J Biol Chem 1996; 271 (13) 7767-73.
    CrossrefPubMedGoogle Scholar
  • 63 Clinton SK, Underwood R, Hayes L, Sherman ML, Kufe DW, Libby P. Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. Am J Pathol 1992; 140 (02) 301-16.
    PubMedGoogle Scholar
  • 64 Liao HS, Matsumoto A, Itakura H, Doi T, Honda M, Kodama T. et al. Transcriptional inhibition by interleukin-6 of the class A macrophage scavenger receptor in macrophages derived from human peripheral monocytes and the THP-1 monocytic cell line. Arterioscler Thromb Vasc Biol 1999; 19 (08) 1872-80.
    CrossrefPubMedGoogle Scholar
  • 65 Geng YJ, Holm J, Nygren S, Bruzelius M, Stemme S, Hansson GK. Expression of the macrophage scavenger receptor in atheroma. Relationship to immune activation and the T-cell cytokine interferon-gamma. Arterioscler Thromb Vasc Biol 1995; 15 (11) 1995-2002.
    CrossrefPubMedGoogle Scholar
  • 66 Li H, Freeman MW, Libby P. Regulation of smooth muscle cell scavenger receptor expression in vivo by atherogenic diets and in vitro by cytokines. J Clin Invest 1995; 95 (01) 122-33.
    CrossrefPubMedGoogle Scholar
  • 67 Wang N, Tabas I, Winchester R, Ravalli S, Rabbani LE, Tall A. Interleukin 8 is induced by cholesterol loading of macrophages and expressed by macrophage foam cells in human atheroma. J Biol Chem 1996; 271 (15) 8837-42.
    CrossrefPubMedGoogle Scholar
  • 68 Janabi M, Yamashita S, Hirano K, Sakai N, Hiraoka H, Matsumoto K. et al. Oxidized LDL-induced NF-kappa B activation and subsequent expression of proinflammatory genes are defective in monocyte-derived macrophages from CD36-deficient patients. Arterioscler Thromb Vasc Biol 2000; 20 (08) 1953-60.
    CrossrefPubMedGoogle Scholar
  • 69 Zoellner H, Filonzi EL, Stanton HR, Layton JE, Hamilton JA. Human arterial smooth muscle cells synthesize granulocyte colony-stimulating factor in response to interleukin-1 alpha and tumor necrosis factor-alpha. Blood 1992; 80 (11) 2805-10.
    PubMedGoogle Scholar
  • 70 Klingemann HG. Clinical applications of recombinant human colonystimulating factors. Cmaj 1989; 140 (02) 137-42.
    PubMedGoogle Scholar
  • 71 Truran L, Baines P, Hoy T, Burnett AK. GCSF augments post-progenitor proliferation in serum-free cultures of myelodysplastic marrow while ATRA enhances maturation. Leuk Res 1998; 22 (03) 241-8.
    CrossrefPubMedGoogle Scholar
  • 72 Filonzi EL, Zoellner H, Stanton H, Hamilton JA. Cytokine regulation of granulocyte-macrophage colony stimulating factor and macrophage colony-stimulating factor production in human arterial smooth muscle cells. Atherosclerosis 1993; 99 (02) 241-52.
    CrossrefPubMedGoogle Scholar
  • 73 Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M. Decreased atherosclerosis in mice deficient in both macrophage colonystimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci USA 1995; 92 (18) 8264-8.
    CrossrefPubMedGoogle Scholar
  • 74 Rajavashisth TB, Andalibi A, Territo MC, Berliner JA, Navab M, Fogelman AM. et al. Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified lowdensity lipoproteins. Nature 1990; 344: 254-57.
    CrossrefPubMedGoogle Scholar
  • 75 Rajavashisth TB, Yamada H, Mishra NK. Transcriptional activation of the macrophage-colony stimulating factor gene by minimally modified LDL. Involvement of nuclear factor-kappa B. Arterioscler Thromb Vasc Biol 1995; 15 (10) 1591-8.
    CrossrefPubMedGoogle Scholar
  • 76 Myllarniemi M, Calderon L, Lemstrom K, Buchdunger E, Hayry P. Inhibition of platelet-derived growth factor receptor tyrosine kinase inhibits vascular smooth muscle cell migration and proliferation. Faseb J 1997; 11 (13) 1119-26.
    CrossrefPubMedGoogle Scholar
  • 77 Hansson GK, Jonasson L, Holm J, Clowes MK, Clowes A. Gamma interferon regulates vascular smooth muscle proliferation and Ia expression in vivo and in vitro. Circ. Research 1988; 63: 712-19.
    PubMedGoogle Scholar
  • 78 Friesel R, Komoriya A, Maciag T. Inhibition of endothelial cell proliferation by gamma-interferon. J Cell Biol 1987; 104 (03) 689-96.
    CrossrefPubMedGoogle Scholar
  • 79 Warner SJC, Friedman GB, Libby P. Immune interferon inhibits proliferation and induces 2’-5’-Oligoadenylate synthetase gene expression in human vascular smooth muscle cells. J Clin Invest 1989; 83: 1174-82.
    CrossrefPubMedGoogle Scholar
  • 80 Kawakami K, Hossain MQureshi, Zhang T, Koguchi Y, Xie Q, Kurimoto M. et al. Interleukin-4 weakens host resistance to pulmonary and disseminated cryptococcal infection caused by combined treatment with interferon-gamma-inducing cytokines. Cell Immunol 1999; 197 (01) 55-61.
    CrossrefPubMedGoogle Scholar
  • 81 Schindler H, Lutz MB, Rollinghoff M, Bogdan C. The production of IFNgamma by IL-12/IL-18-activated macrophages requires STAT4 signaling and is inhibited by IL-4. J Immunol 2001; 166 (05) 3075-82.
    CrossrefPubMedGoogle Scholar
  • 82 Gehrmann J. Colony-stimulating factors regulate programmed cell death of rat microglia/brain macrophages in vitro. J Neuroimmunol 1995; 63 (01) 55-61.
    CrossrefPubMedGoogle Scholar
  • 83 Munn DH, Beall AC, Song D, Wrenn RW, Throckmorton DC. Activationinduced apoptosis in human macrophages: developmental regulation of a novel cell death pathway by macrophage colony-stimulating factor and interferon gamma. J Exp Med 1995; 181 (01) 127-36.
    CrossrefPubMedGoogle Scholar
  • 84 Bennett MR, Evan GI, Schwartz SM. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Invest 1995; 95 (05) 2266-74.
    CrossrefPubMedGoogle Scholar
  • 85 Newby AC, George SJ. Proliferation, migration, matrix turnover, and death of smooth muscle cells in native coronary and vein graft atherosclerosis. Curr Opin Cardiol 1996; 11 (06) 574-82.
    CrossrefPubMedGoogle Scholar
  • 86 Cai W, Devaux B, Schaper W, Schaper J. The role of Fas/APO 1 and apoptosis in the development of human atherosclerotic lesions. Atherosclerosis 1997; 131 (02) 177-86.
    CrossrefPubMedGoogle Scholar
  • 87 Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol 1995; 146 (01) 3-15.
    PubMedGoogle Scholar
  • 88 Li PF, Maasch C, Haller H, Dietz R, von Harsdorf R. Requirement for protein kinase C in reactive oxygen species-induced apoptosis of vascular smooth muscle cells. Circulation 1999; 100 (09) 967-73.
    CrossrefPubMedGoogle Scholar
  • 89 Geng YJ, Wu Q, Muszynski M, Hansson GK, Libby P. Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. Arterioscler Thromb Vasc Biol 1996; 16 (01) 19-27.
    CrossrefPubMedGoogle Scholar
  • 90 Fukuo K, Nakahashi T, Nomura S, Hata S, Suhara T, Shimizu M. et al. Possible participation of Fas-mediated apoptosis in the mechanism of atherosclerosis. Gerontology 1997; 43 (Suppl. 01) 35-42.
    CrossrefPubMedGoogle Scholar
  • 91 Fukuo K, Suhara T, Nakahashi T, Hata S, Shimizu M, Niinobu T. et al. Activated T cells induce up-regulation of Fas antigen in cultured endothelial cells. Heart Vessels 1997; Suppl (12) 81-3.
    PubMedGoogle Scholar
  • 92 Chinetti G, Griglio S, Antonucci M, Torra IP, Delerive P, Majd Z. et al. Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages. J Biol Chem 1998; 273 (40) 25573-80.
    CrossrefPubMedGoogle Scholar
  • 93 Lee YW, Kuhn H, Hennig B, Toborek M. IL-4 induces apoptosis of endothelial cells through the caspase-3-dependent pathway. FEBS Lett 2000; 485 2-3 122-6.
    CrossrefPubMedGoogle Scholar
  • 94 Lindner H, Holler E, Ertl B, Multhoff G, Schreglmann M, Klauke I. et al. Peripheral blood mononuclear cells induce programmed cell death in human endothelial cells and may prevent repair: role of cytokines. Blood 1997; 89 (06) 1931-8.
    PubMedGoogle Scholar
  • 95 Saito I. Structure of IL-10 and its role in autoimmune exocrinopathy. Crit Rev Immunol 2000; 20 (02) 153-65.
    PubMedGoogle Scholar
  • 96 Taga K, Cherney B, Tosato G. IL-10 inhibits apoptotic cell death in human T cells starved of IL-2. Int Immunol 1993; 05 (12) 1599-608.
    CrossrefPubMedGoogle Scholar
  • 97 Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995; 91 (11) 2844-50.
    CrossrefPubMedGoogle Scholar
  • 98 Amento EP, Ehsani N, Palmer H, Libby P. Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. Arterioscler Thromb 1991; 11 (05) 1223-30.
    CrossrefPubMedGoogle Scholar
  • 99 Rekhter MD, Zhang K, Narayanan AS, Phan S, Schork MA, Gordon D. Type I collagen gene expression in human atherosclerosis. Localization to specific plaque regions. Am J Pathol 1993; 143 (06) 1634-48.
    PubMedGoogle Scholar
  • 100 Mitchell PG, Magna HA, Reeves LM, Lopresti-Morrow LL, Yocum SA, Rosner PJ. et al. Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest 1996; 97 (03) 761-8.
    CrossrefPubMedGoogle Scholar
  • 101 Billinghurst RC, Dahlberg L, Ionescu M, Reiner A, Bourne R, Rorabeck C. et al. Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J Clin Invest 1997; 99 (07) 1534-45.
    CrossrefPubMedGoogle Scholar
  • 102 Sukhova GK, Schonbeck U, Rabkin E, Schoen FJ, Poole AR, Billinghurst RC. et al. Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. Circulation 1999; 99 (19) 2503-9.
    CrossrefPubMedGoogle Scholar
  • 103 Richardson PD, Davies MJ, Born GV. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques [see comments]. Lancet 1989; 02 8669 941-4.
    PubMedGoogle Scholar
  • 104 Herman MP, Sukhova GK, Libby P, Gerdes N, Tang N, Horton DB. et al. Expression of neutrophil collagenase (matrix metalloproteinase-8) in human atheroma: a novel collagenolytic pathway suggested by transcriptional profiling. Circulation 2001; 104 (16) 1899-904.
    CrossrefPubMedGoogle Scholar
  • 105 Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Unemori EN, Lark MW. et al. Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res 1994; 75 (01) 181-9.
    CrossrefPubMedGoogle Scholar
  • 106 Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E, Libby P. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann N Y Acad Sci 1995; 748: 501-7.
    PubMedGoogle Scholar
  • 107 Schonbeck U, Mach F, Sukhova GK, Murphy C, Bonnefoy JY, Fabunmi RP. et al. Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes: a role for CD40 signaling in plaque rupture?. Circ Res 1997; 81 (03) 448-54.
    CrossrefPubMedGoogle Scholar
  • 108 Fabunmi RP, Libby P. Regulation of Metalloproteinases and Their Inhibitors in Atheroma. In: Fuster V. editor. The Vulnerable Atherosclerotic Plaque: Understanding, Identification, and Modification. Armonk, NY: Futura Publishing Company, Inc; 1999: 365-381.
    Google Scholar
  • 109 Schonbeck U, Mach F, Sukhova GK, Atkinson E, Levesque E, Herman M. et al. Expression of stromelysin-3 in atherosclerotic lesions: regulation via CD40-CD40 ligand signaling in vitro and in vivo. J Exp Med 1999; 189 (05) 843-53.
    CrossrefPubMedGoogle Scholar
  • 110 Malik N, Greenfield BW, Wahl AF, Kiener PA. Activation of human monocytes through CD40 induces matrix metalloproteinases. J Immunol 1996; 156 (10) 3952-60.
    PubMedGoogle Scholar
  • 111 Mach F, Schonbeck U, Bonnefoy JY, Pober JS, Libby P. Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor. Circulation 1997; 96 (02) 396-9.
    CrossrefPubMedGoogle Scholar
  • 112 Lacraz S, Nicod L, Galve-de Rochemonteix B, Baumberger C, Dayer JM, Welgus HG. Suppression of metalloproteinase biosynthesis in human alveolar macrophages by interleukin-4. J Clin Invest 1992; 90 (02) 382-8.
    CrossrefPubMedGoogle Scholar
  • 113 Okada Y, Gonoji Y, Naka K, Tomita K, Nakanishi I, Iwata K. et al. Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties. J Biol Chem 1992; 267 (30) 21712-9.
    PubMedGoogle Scholar
  • 114 Okada Y, Morodomi T, Enghild JJ, Suzuki K, Yasui A, Nakanishi I. et al. Matrix metalloproteinase 2 from human rheumatoid synovial fibroblasts. Purification and activation of the precursor and enzymic properties. Eur J Biochem 1990; 194 (03) 721-30.
    CrossrefPubMedGoogle Scholar
  • 115 Nagase H, Enghild JJ, Suzuki K, Salvesen G. Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl)mercuric acetate. Biochemistry 1990; 29 (24) 5783-9.
    CrossrefPubMedGoogle Scholar
  • 116 Galis ZS, Kranzhofer R, Fenton 2nd JW, Libby P. Thrombin promotes activation of matrix metalloproteinase-2 produced by cultured vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1997; 17 (03) 483-9.
    CrossrefPubMedGoogle Scholar
  • 117 Lee E, Vaughan DE, Parikh SH, Grodzinsky AJ, Libby P, Lark MW. et al. Regulation of matrix metalloproteinases and plasminogen activator inhibitor-1 synthesis by plasminogen in cultured human vascular smooth muscle cells. Circulation Research 1996; 78 (01) 44-9.
    CrossrefPubMedGoogle Scholar
  • 118 Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. Journal of Clinical Investigation 1996; 98 (11) 2572-9.
    CrossrefPubMedGoogle Scholar
  • 119 Okada Y, Nakanishi I. Activation of matrix metalloproteinase 3 (stromelysin) and matrix metalloproteinase 2 (‘gelatinase’) by human neutrophil elastase and cathepsin G. FEBS Lett 1989; 249 (02) 353-6.
    CrossrefPubMedGoogle Scholar
  • 120 Pei D, Weiss SJ. Furin-dependent intracellular activation of the human stromelysin-3 zymogen. Nature 1995; 375 6528 244-7.
    CrossrefPubMedGoogle Scholar
  • 121 Sato H, Kinoshita T, Takino T, Nakayama K, Seiki M. Activation of a recombinant membrane type 1-matrix metalloproteinase (MT1-MMP) by furin and its interaction with tissue inhibitor of metalloproteinases (TIMP)-2. FEBS Lett 1996; 393 (01) 101-4.
    CrossrefPubMedGoogle Scholar
  • 122 Han YP, Tuan TL, Hughes M, Wu H, Garner WL. Transforming growth factor-beta - and tumor necrosis factor-alpha - mediated induction and proteolytic activation of MMP-9 in human skin. J Biol Chem 2001; 276 (25) 22341-50.
    CrossrefPubMedGoogle Scholar
  • 123 Kubota Y, Ninomiya T, Oka S, Takenoshita Y, Shirasuna K. Interleukin-1alpha-dependent regulation of matrix metalloproteinase-9 (MMP-9) secretion and activation in the epithelial cells of odontogenic jaw cysts. J Dent Res 2000; 79 (06) 1423-30.
    CrossrefPubMedGoogle Scholar
  • 124 Rajavashisth TB, Xu XP, Jovinge S, Meisel S, Xu XO, Chai NN. et al. Membrane type 1 matrix metalloproteinase expression in human atherosclerotic plaques: evidence for activation by proinflammatory mediators. Circulation 1999; 99 (24) 3103-9.
    CrossrefPubMedGoogle Scholar
  • 125 Herman MP, Sukhova GK, Kisiel W, Foster D, Kehry MR, Libby P. et al. Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosis. J Clin Invest 2001; 107 (09) 1117-26.
    CrossrefPubMedGoogle Scholar
  • 126 Fabunmi RP, Baker AH, Murray EJ, Booth RF, Newby AC. Divergent regulation by growth factors and cytokines of 95 kDa and 72 kDa gelatinases and tissue inhibitors or metalloproteinases-1, -2, and -3 in rabbit aortic smooth muscle cells. Biochem J 1996; 315 Pt 1 335-42.
    CrossrefPubMedGoogle Scholar
  • 127 Horton DB, Libby P, Schonbeck U. Ligation of CD40 onvascular smooth muscle cells mediates loss of interstitial collagen via matrix metalloproteinase activity. Ann N Y Acad Sci 2001; 947: 329-36.
    PubMedGoogle Scholar
  • 128 Toschi V, Gallo R, Lettino M, Fallon JT, Gertz SD, Fernandez-Ortiz A. et al. Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997; 95 (03) 594-9.
    CrossrefPubMedGoogle Scholar
  • 129 Moreno PR, Bernardi VH, Lopez-Cuellar J, Murcia AM, Palacios IF, Gold HK. et al. Macrophages, smooth muscle cells, and tissue factor in unstable angina. Implications for cell-mediated thrombogenicity in acute coronary syndromes. Circulation 1996; 94 (12) 3090-7.
    CrossrefPubMedGoogle Scholar
  • 130 Taubman MB, Fallon JT, Schecter AD, Giesen P, Mendlowitz M, Fyfe BS. et al. Tissue factor in the pathogenesis of atherosclerosis. Thromb Haemost 1997; 78 (01) 200-4.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 131 Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1989; 86 (08) 2839-43.
    CrossrefPubMedGoogle Scholar
  • 132 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol 1989; 134 (05) 1087-97.
    PubMedGoogle Scholar
  • 133 Schecter AD, Rollins BJ, Zhang YJ, Charo IF, Fallon JT, Rossikhina M. et al. Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells. J Biol Chem 1997; 272 (45) 28568-73.
    CrossrefPubMedGoogle Scholar
  • 134 Osnes LT, Westvik AB, Joo GB, Okkenhaug C, Kierulf P. Inhibition of IL-1 induced tissue factor (TF) synthesis and procoagulant activity (PCA) in purified human monocytes by IL-4, IL-10 and IL-13. Cytokine 1996; 08 (11) 822-7.
    CrossrefPubMedGoogle Scholar
  • 135 Taubman MB. Tissue factor regulation in vascular smooth muscle: a summary of studies performed using in vivo and in vitro models. Am J Cardiol 1993; 72 (08) 55C-60C.
    CrossrefPubMedGoogle Scholar
  • 136 Zhou L, Stordeur P, de Lavareille A, Thielemans K, Capel P, Goldman M. et al. CD40 engagement on endothelial cells promotes tissue factor-dependent procoagulant activity. Thromb Haemost 1998; 79 (05) 1025-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 137 Miller DL, Yaron R, Yellin MJ. CD40L-CD40 interactions regulate endothelial cell surface tissue factor and thrombomodulin expression. J Leukoc Biol 1998; 63 (03) 373-9.
    CrossrefPubMedGoogle Scholar
  • 138 Schonbeck U, Mach F, Sukhova GK, Herman M, Graber P, Kehry MR. et al. CD40 ligation induces tissue factor expression in human vascular smooth muscle cells. Am J Pathol 2000; 156 (01) 7-14.
    CrossrefPubMedGoogle Scholar
  • 139 Aikawa M, Voglic SJ, Sugiyama S, Rabkin E, Taubman MB, Fallon JT. et al. Dietary lipid lowering reduces tissue factor expression in rabbit atheroma. Circulation 1999; 100 (11) 1215-22.
    CrossrefPubMedGoogle Scholar
  • 140 Kato K, Elsayed YA, Namoto M, Nakagawa K, Sueishi K. Enhanced expression of tissue factor activity in the atherosclerotic aortas of holesterol-fed rabbits. Thromb Res 1996; 82 (04) 335-47.
    CrossrefPubMedGoogle Scholar
  • 141 Noble KE, Harkness D, Yong KL. Interleukin 10 regulates cellular responses in monocyte/endothelial cell co-cultures. Br J Haematol 2000; 108 (03) 497-504.
    CrossrefPubMedGoogle Scholar
  • 142 Chu AJ, Prasad JK. Antagonism by IL-4 and IL-10 of endotoxin-induced tissue factor activation in monocytic THP-1 cells: activating role of CD14 ligation. J Surg Res 1998; 80 (01) 80-7.
    CrossrefPubMedGoogle Scholar
  • 143 Lindmark E, Tenno T, Chen J, Siegbahn A. IL-10 inhibits LPS-induced human monocyte tissue factor expression in whole blood. Br J Haematol 1998; 102 (02) 597-604.
    CrossrefPubMedGoogle Scholar
  • 144 Ernofsson M, Tenno T, Siegbahn A. Inhibition of tissue factor surface expression in human peripheral blood monocytes exposed to cytokines. Br J Haematol 1996; 95 (02) 249-57.
    CrossrefPubMedGoogle Scholar
  • 145 Jungi TW, Brcic M, Eperon S, Albrecht S. Transforming growth factorbeta and interleukin-10, but not interleukin-4, down-regulate procoagulant activity and tissue factor expression in human monocyte-derived macrophages. Thromb Res 1994; 76 (05) 463-74.
    CrossrefPubMedGoogle Scholar
  • 146 Schwager I, Jungi TW. Effect of human recombinant cytokines on the induction of macrophage procoagulant activity. Blood 1994; 83 (01) 152-60.
    PubMedGoogle Scholar
  • 147 Martin NB, Jamieson A, Tuffin DP. The effect of interleukin-4 on tumour necrosis factor-alpha induced expression of tissue factor and plasminogen activator inhibitor-1 in human umbilical vein endothelial cells. Thromb Haemost 1993; 70 (06) 1037-42.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 148 Herbert JM, Savi P, Laplace MC, Lale A. IL-4 inhibits LPS-, IL-1 beta-and TNF alpha-induced expression of tissue factor in endothelial cells and monocytes. FEBS Lett 1992; 310 (01) 31-3.
    CrossrefPubMedGoogle Scholar
  • 149 Pradier O, Willems F, Abramowicz D, Schandene L, de Boer M, Thielemans K. et al. CD40 engagement induces monocyte procoagulant activity through an interleukin-10 resistant pathway. Eur J Immunol 1996; 26 (12) 3048-54.
    CrossrefPubMedGoogle Scholar
  • 150 Kaikita K, Takeya M, Ogawa H, Suefuji H, Yasue H, Takahashi K. Colocalization of tissue factor and tissue factor pathway inhibitor in coronary atherosclerosis. J Pathol 1999; 188 (02) 180-8.
    CrossrefPubMedGoogle Scholar
  • 151 Shah PK. Plaque disruption and thrombosis. Potential role of inflammation and infection. Cardiol Clin 1999; 17 (02) 271-81.
    CrossrefPubMedGoogle Scholar
  • 152 Kinlay S, Selwyn AP, Libby P, Ganz P. Inflammation, the endothelium, and the acute coronary syndromes. J Cardiovasc Pharmacol 1998; 32 (Suppl. 03) S62-6.
    CrossrefPubMedGoogle Scholar
  • 153 Becker BF, Heindl B, Kupatt C, Zahler S. Endothelial function and hemostasis. Z Kardiol 2000; 89 (03) 160-7.
    PubMedGoogle Scholar
  • 154 Nachman RL, Hajjar KA, Silverstein RL, Dinarello CA. Interleukin 1 induces endothelial cell synthesis of plasminogen activator inhibitor. J Exp Med 1986; 163 (06) 1595-600.
    CrossrefPubMedGoogle Scholar
  • 155 Zoellner H, Wojta J, Gallicchio M, McGrath K, Hamilton JA. Cytokine regulation of the synthesis of plasminogen activator inhibitor-2 by human vascular endothelial cells. Comparison with plasminogen activator inhibitor-1 synthesis. Thromb Haemost 1993; 69 (02) 135-40.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 156 Gallicchio M, Hufnagl P, Wojta J, Tipping P. IFN-gamma inhibits thrombin-and endotoxin-induced plasminogen activator inhibitor type 1 in human endothelial cells. J Immunol 1996; 157 (06) 2610-7.
    PubMedGoogle Scholar
  • 157 Arnman V, Stemme S, Rymo L, Risberg B. Interferon-gamma modulates the fibrinolytic response in cultured human endothelial cells. Thromb Res 1995; 77 (05) 431-40.
    CrossrefPubMedGoogle Scholar
  • 158 Kapiotis S, Besemer J, Bevec D, Valent P, Bettelheim P, Lechner K. et al. Interleukin-4 counteracts pyrogen-induced downregulation of thrombomodulin in cultured human vascular endothelial cells. Blood 1991; 78 (02) 410-5.
    PubMedGoogle Scholar
  • 159 Dalekos GN, Elisaf M, Bairaktari E, Tsolas O, Siamopoulos KC. Increased serum levels of interleukin-1beta in the systemic circulation of patients with essential hypertension: additional risk factor for atherogenesis in hypertensive patients?. J Lab Clin Med 1997; 129 (03) 300-8.
    CrossrefPubMedGoogle Scholar
  • 160 Balbay Y, Tikiz H, Baptiste RJ, Ayaz S, Sasmaz H, Korkmaz S. Circulating interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and soluble ICAM-1 in patients with chronic stable angina and myocardial infarction. Angiology 2001; 52 (02) 109-14.
    CrossrefPubMedGoogle Scholar
  • 161 Aukrust P, Muller F, Ueland T, Berget T, Aaser E, Brunsvig A. et al. Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina. Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes. Circulation 1999; 100 (06) 614-20.
    CrossrefPubMedGoogle Scholar
  • 162 Koenig W, Sund M, Frohlich M, Fischer HG, Lowel H, Doring A. et al. C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999; 99 (02) 237-42.
    CrossrefPubMedGoogle Scholar
  • 163 Koenig W. Inflammation and coronary heart disease: an overview. Cardiol Rev 2001; 09 (01) 31-5.
    CrossrefPubMedGoogle Scholar
  • 164 Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342 (12) 836-43.
    CrossrefPubMedGoogle Scholar
  • 165 Ridker PM. Role of inflammatory biomarkers in prediction of coronary heart disease. Lancet 2001; 358 9286 946-8.
    CrossrefPubMedGoogle Scholar
  • 166 Schonbeck U, Varo N, Libby P, Buring J, Ridker PM. Soluble CD40L and cardiovascular risk in women. Circulation 2001; 104 (19) 2266-8.
    CrossrefPubMedGoogle Scholar
  • 167 Interleukin Genetics – Coronary Artery Disease. In.: pnInterleukin Genetics, Inc..
  • 168 Basso F, Lowe GD, Rumley A, McMahon AD, Humphries SE. Interleukin-6 -174G>C polymorphism and risk of coronary heart disease in West of Scotland coronary prevention study (WOSCOPS). Arterioscler Thromb Vasc Biol 2002; 22 (04) 599-604.
    CrossrefPubMedGoogle Scholar
  • 169 Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet 1996; 348 9034 1079-82.
    CrossrefPubMedGoogle Scholar
  • 170 Dangas G, Smith DA, Unger AH, Shao JH, Meraj P, Fier C. et al. Pravastatin: an antithrombotic effect independent of the cholesterollowering effect. Thromb Haemost 2000; 83 (05) 688-92.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 171 Ni W, Egashira K, Kataoka C, Kitamoto S, Koyanagi M, Inoue S. 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 (05) 415-21.
    CrossrefPubMedGoogle Scholar
  • 172 Heeschen C, Hamm CW, Laufs U, Snapinn S, Bohm M, White HD. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation 2002; 105 (12) 1446-52.
    CrossrefPubMedGoogle Scholar
  • 173 Musial J, Undas A, Gajewski P, Jankowski M, Sydor W, Szczeklik A. Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia. Int J Cardiol 2001; 77 2-3 247-53.
    CrossrefPubMedGoogle Scholar
  • 174 Takata M, Urakaze M, Temaru R, Yamazaki K, Nakamura N, Nobata Y. et al. Pravastatin suppresses the interleukin-8 production induced by thrombin in human aortic endothelial cells cultured with high glucose by inhibiting the p44/42 mitogen activated protein kinase. Br J Pharmacol 2001; 134 (04) 753-62.
    CrossrefPubMedGoogle Scholar
  • 175 Grip O, Janciauskiene S, Lindgren S. Pravastatin down-regulates inflammatory mediators in human monocytes in vitro. Eur J Pharmacol 2000; 410 (01) 83-92.
    CrossrefPubMedGoogle Scholar
  • 176 Kiener PA, Davis PM, Murray JL, Youssef S, Rankin BM, Kowala M. Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors. Int Immunopharmacol 2001; 01 (01) 105-18.
    CrossrefPubMedGoogle Scholar
  • 177 Libby P, Aikawa M, Schönbeck U. Cholesterol and atherosclerosis. Biochim Biophys Acta 2000; 1529 1-3 299-309.
    CrossrefPubMedGoogle Scholar
  • 178 Lopez S, Peiretti F, Bonardo B, Juhan-Vague I, Nalbone G. Effect of atorvastatin and fluvastatin on the expression of plasminogen activator inhibitor type-1 in cultured human endothelial cells. Atherosclerosis 2000; 152 (02) 359-66.
    CrossrefPubMedGoogle Scholar
  • 179 Aikawa M, Rabkin E, Okada Y, Voglic SJ, Clinton SK, Brinckerhoff CE. et al. Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. Circulation 1998; 97 (24) 2433-44.
    CrossrefPubMedGoogle Scholar
  • 180 Aikawa M, Rabkin E, Sugiyama S, Voglic SJ, Fukumoto Y, Furukawa Y. et al. An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro. Circulation 2001; 103 (02) 276-83.
    CrossrefPubMedGoogle Scholar
  • 181 Bustos C, Hernandez-Presa MA, Ortego M, Tunon J, Ortega L, Perez F. et al. HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis. J Am Coll Cardiol 1998; 32 (07) 2057-64.
    CrossrefPubMedGoogle Scholar
  • 182 Knapp AC, Huang J, Starling G, Kiener PA. Inhibitors of HMG-CoA reductase sensitize human smooth muscle cells to Fas-ligand and cytokineinduced cell death. Atherosclerosis 2000; 152 (01) 217-27.
    CrossrefPubMedGoogle Scholar
  • 183 Murphy RT, Foley JB, Mulvihill N, Crean P, Walsh MJ. Impact of preexisting statin use on adhesion molecule expression in patients presenting with acute coronary syndromes. Am J Cardiol 2001; 87 (04) 446-8 A6.
    CrossrefPubMedGoogle Scholar
  • 184 Laufs U, Gertz K, Huang P, Nickenig G, Bohm M, Dirnagl U. et al. Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke 2000; 31 (10) 2442-9.
    CrossrefPubMedGoogle Scholar