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Cardiac Drug Development Guide pp 87–105Cite as

Development of Anti-Inflammatory Drugs for Cardiovascular Disease

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Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Cardiovascular disease is the leading cause of death in the United States. One in three men and one in ten women develop severe cardiovascular disease before the age of 60, resulting in health expenditures of over $100 billion per year. Even though cardiovascular disease primarily affects people advanced in age, disease progression begins early. Initiation of atherogenesis via formation of fatty streaks can occur as early as infancy (1).

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References

  1. Napoli, C., D’Armiento, F. P., Mancini, F. P., Postiglione, A., Witztum, J. L., Palumbo, G., et al. (1997) Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J. Clin Invest. 100, 2680–2690.

    Article  PubMed  CAS  Google Scholar 

  2. Stary, H. C., Chandler, A. B., Glagov, S., Guyton, J. R., Insull, W., Jr., Rosenfeld, M. E., et al. (1994) A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 89, 2462–2478.

    PubMed  CAS  Google Scholar 

  3. Jonasson, L., Holm, J., Skalli, O., Bondjers, G., and Hansson, G. K. (1986) Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis 6, 131–138.

    PubMed  CAS  Google Scholar 

  4. van der Wal, A. C., Das, P. K., Bentz, V. B., van der Loos, C. M., and Becker, A. E. (1989) Atherosclerotic lesions in humans. In situ immunophenotypic analysis suggesting an immune mediated response. Lab. Invest. 61, 166–170.

    PubMed  Google Scholar 

  5. McLenachan, J. M., Williams, J. K., Fish, R. D., Ganz, P., and Selwyn, A. P. (1991) Loss of flow-mediated endothelium-dependent dilation occurs early in the development of atherosclerosis. Circulation 84, 1273–1278.

    PubMed  CAS  Google Scholar 

  6. Kinlay, S. and Ganz, P. (1997) Role of endothelial dysfunction in coronary artery disease and implications for therapy. Am. J. Cardiol. 80, 11I–16I.

    Article  PubMed  CAS  Google Scholar 

  7. Morel, D. W., Hessler, J. R., and Chisolm, G. M. (1983) Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid. J. Lipid Res. 24, 1070–1076.

    PubMed  CAS  Google Scholar 

  8. Griendling, K. K. and Alexander, R. W. (1997) Oxidative stress and cardiovascular disease. Circulation 96, 3264–3265.

    PubMed  CAS  Google Scholar 

  9. Swei, A., Lacy, F., DeLano, F. A., and Schmid-Schonbein, G. W. (1997) Oxidative stress in the Dahl hypertensive rat. Hypertension 30, 1628–1633.

    PubMed  CAS  Google Scholar 

  10. Vanhoutte, P. M. and Boulanger, C. M. (1995) Endothelium-dependent responses in hypertension. Hypertens. Res. 18, 87–98.

    Article  PubMed  CAS  Google Scholar 

  11. Hajjar, K. A. (1993) Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor. J. Clin Invest. 91, 2873–2879.

    Article  PubMed  CAS  Google Scholar 

  12. Harker, L. A., Ross, R., Slichter, S. J., and Scott, C. R. (1976) Homocystine-induced arteriosclerosis. The role of endothelial cell injury and platelet response in its genesis. J. Clin Invest. 58, 731–741.

    Article  PubMed  CAS  Google Scholar 

  13. Upchurch, G. R., Jr., Welch, G. N., Fabian, A. J., Freedman, J. E., Johnson, J. L., Keaney, J. F., Jr., et al. (1997) Homocysteine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J. Biol. Chem. 272, 17012–17017.

    Article  PubMed  CAS  Google Scholar 

  14. Majors, A., Ehrhart, L. A., and Pezacka, E. H. (1997) Homocysteine as a risk factor for vascular disease. Enhanced collagen production and accumulation by smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 17, 2074–2081.

    PubMed  CAS  Google Scholar 

  15. Bellamy, M. F., McDowell, I. F., Ramsey, M. W., Brownlee, M., Bones, C., Newcombe, R. G., et al. (1998) Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults. Circulation 98, 1848–1852.

    PubMed  CAS  Google Scholar 

  16. Quyyumi, A. A., Dakak, N., Andrews, N. P., Husain, S., Arora, S., Gilligan, D. M., et al. (1995) Nitric oxide activity in the human coronary Circulation. Impact of risk factors for coronary atherosclerosis. J. Clin Invest. 95, 1747–1755.

    Article  PubMed  CAS  Google Scholar 

  17. Gimbrone, M. A., Jr., Topper, J. N., Nagel, T., Anderson, K. R., and Garcia-Cardena, G. (2000) Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann. N. Y. Acad. Sci. 902, 230–239.

    Article  PubMed  CAS  Google Scholar 

  18. Topper, J. N. and Gimbrone, M. A., Jr. (1999) Blood flow and vascular gene expression: Fluid shear stress as a modulator of endothelial phenotype. Mol. Med. Today 5, 40–46.

    Article  PubMed  CAS  Google Scholar 

  19. Libby, P., Friedman, G. B., and Salomon, R. N. (1989) Cytokines as modulators of cell proliferation in fibrotic diseases. Am. Rev. Respir. Dis. 140, 1114–1117.

    PubMed  CAS  Google Scholar 

  20. Raines, E. W., Dower, S. K., and Ross, R. (1989) Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science 243, 393–396.

    Article  PubMed  CAS  Google Scholar 

  21. Old, L. J. (1985) Tumor necrosis factor (TNF). Science 230, 630–632.

    Article  PubMed  CAS  Google Scholar 

  22. Amento, E. P., Ehsani, N., Palmer, H., and Libby, P. (1991) Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. Arterioscler. Thromb. 11, 1223–1230.

    PubMed  CAS  Google Scholar 

  23. Libby, P, Warner, S. J., and Friedman, G. B. (1988) Interleukin 1: A mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J. Clin. Invest. 81, 487–498.

    Article  PubMed  CAS  Google Scholar 

  24. Cybulsky, M. I. and Gimbrone, M. A., Jr. (1991) Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 251, 788–791.

    Article  PubMed  CAS  Google Scholar 

  25. Bevilacqua, M. P., Stengelin, S., Gimbrone, M. A., Jr., and Seed, B. (1989) Endothelial leukocyte adhesion molecule 1: An inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 243, 1160–1165.

    Article  PubMed  CAS  Google Scholar 

  26. Pober, J. S. and Cotran, R. S. (1990) Cytokines and endothelial cell biology. Physiol. Rev. 70, 427–451.

    PubMed  CAS  Google Scholar 

  27. Loppnow, H. and Libby, P. (1990) Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6. J. Clin Invest. 85, 731–738.

    Article  PubMed  CAS  Google Scholar 

  28. Valente, A. J., Graves, D. T., Vialle-Valentin, C. E., Delgado, R., and Schwartz, C. J. (1988) Purification of a monocyte chemotactic factor secreted by nonhuman primate vascular cells in culture. Biochemistry 27, 4162–4168.

    Article  PubMed  CAS  Google Scholar 

  29. Gay, C. G., and Winkles, J. A. (1991) Interleukin 1 regulates heparin-binding growth factor 2 gene expression in vascular smooth muscle cells. Proc. Natl. Acad. Sci. USA 88, 296–300.

    Article  PubMed  CAS  Google Scholar 

  30. Warner, S. J., Friedman, G. B., and Libby, P. (1989) Regulation of major histocompatibility gene expression in human vascular smooth muscle cells. Arteriosclerosis 9, 279–288.

    PubMed  CAS  Google Scholar 

  31. Galis, Z. S., Muszynski, M., Sukhova, G. K., Simon-Morrissey, E., Unemori, E. N., Lark, M. W., et al. (1994) Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ. Res. 75, 181–189.

    PubMed  CAS  Google Scholar 

  32. Battegay, E. J., Raines, E. W., Seifert, R. A., Bowen-Pope, D. F., and Ross, R. (1990) TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. Cell 63, 515–524.

    Article  PubMed  CAS  Google Scholar 

  33. Moses, H. L., Yang, E. Y., and Pietenpol, J. A. (1990) TGF-beta stimulation and inhibition of cell proliferation: New mechanistic insights. Cell 63, 245–247.

    Article  PubMed  CAS  Google Scholar 

  34. Butcher, E. C. (1991) Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity. Cell 67, 1033–1036.

    Article  PubMed  CAS  Google Scholar 

  35. Lorant, D. E., Patel, K. D., McIntyre, T. M., McEver, R. P., Prescott, S. M., and Zimmerman, G. A. (1991) Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: A juxtacrine system for adhesion and activation of neutrophils. J. Cell. Biol. 115, 223–234.

    Article  PubMed  CAS  Google Scholar 

  36. Dustin, M. L., Rothlein, R., Bhan, A. K., Dinarello, C. A., and Springer, T. A. (1986) Induction by IL 1 and interferon-gamma: Tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J. Immunol. 137, 245–254.

    PubMed  CAS  Google Scholar 

  37. Bevilacqua, M. P., Pober, J. S., Mendrick, D. L., Cotran, R. S., and Gimbrone, M. A., Jr. (1987) Identification of an inducible endothelial-leukocyte adhesion molecule. Proc. Natl. Acad. Sci. USA 84, 9238–9242.

    Article  PubMed  CAS  Google Scholar 

  38. Munro, J. M., Pober, J. S., and Cotran, Ra. S. (1989) Tumor necrosis factor and interferongamma induce distinct patterns of endothelial activation and associated leukocyte accumulation in skin of Papio anubis. Am. J. Pathol. 135, 121–133.

    PubMed  CAS  Google Scholar 

  39. Cotran, R. S., Gimbrone, M. A., Jr., Bevilacqua, M. P., Mendrick, D. L., and Pober, J. S. (1986) Induction and detection of a human endothelial activation antigen in vivo. J. Exp. Med. 164, 661–666.

    Article  PubMed  CAS  Google Scholar 

  40. Lo, S. K., Detmers, P. A., Levin, S. M., and Wright, S. D. (1989) Transient adhesion of neutrophils to endothelium. J. Exp. Med. 169, 1779–1793.

    Article  PubMed  CAS  Google Scholar 

  41. Gamble, J. R., Harlan, J. M., Klebanoff, S. J., and Vadas, M. A. (1985) Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc. Natl. Acad. Sci. USA 82, 8667–8671.

    Article  PubMed  CAS  Google Scholar 

  42. Miller, L. J., Bainton, D. F., Borregaard, N., and Springer, T. A. (1987) Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface. J. Clin. Invest. 80, 535–544.

    Article  PubMed  CAS  Google Scholar 

  43. Werb, Z. and Gordon, S. (1975) Secretion of a specific collagenase by stimulated macrophages. J. Exp. Med. 142, 346–360.

    Article  PubMed  CAS  Google Scholar 

  44. Mainardi, C. L., Seyer, J. M., and Kang, A. H. (1980) Type-specific collagenolysis: a type V collagen-degrading enzyme from macrophages. Biochem. Biophys. Res. Commun. 97, 1108–1115.

    Article  PubMed  CAS  Google Scholar 

  45. Werb, Z., Gordon, S. (1975) Elastase secretion by stimulated macrophages. Characterization and regulation. J. Exp. Med. 142, 361–377.

    Article  PubMed  CAS  Google Scholar 

  46. Hajjar, K. A., Hajjar, D. P., Silverstein, R. L., and Nachman, R. L. (1987) Tumor necrosis factor-mediated release of platelet-derived growth factor from cultured endothelial cells. J. Exp. Med. 166, 235–245.

    Article  PubMed  CAS  Google Scholar 

  47. Leonard, E. J. and Yoshimura, T. (1990) Human monocyte chemoattractant protein-1 (MCP-1). Immunol. Today 11, 97–101.

    Article  PubMed  CAS  Google Scholar 

  48. Bjorkerud, S. and Bjorkerud, B. (1996) Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. Am. J. Pathol. 149, 367–380.

    PubMed  CAS  Google Scholar 

  49. Munro, J. M. and Cotran, R. S. (1998) The pathogenesis of atherosclerosis: Atherogenesis and inflammation. Lab. Invest. 58, 249–261.

    Google Scholar 

  50. Campbell, G. R., Campbell, J. H., Manderson, J. A., Horrigan, S., and Rennick, R. E. (1988) Arterial smooth muscle. A multifunctional mesenchymal cell. Arch. Pathol. Lab. Med. 112, 977–986.

    PubMed  CAS  Google Scholar 

  51. Henney, A. M., Wakeley, P. R., Davies, M. J., Foster, K., Hembry, R., Murphy, G., et al. (1991) Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. Proc. Natl. Acad. Sci. USA 88, 8154–8158.

    Article  PubMed  CAS  Google Scholar 

  52. Galis, Z.S, Sukhova, G. K., Lark, M. W., and Libby, P. (1994) Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J. Clin Invest. 94, 2493–2503.

    Article  PubMed  CAS  Google Scholar 

  53. Windsor, A. C., Walsh, C. J., Mullen, P. G., Cook, D. J., Fisher, B. J., Blocher, C. R., et al. (1993) Tumor necrosis factor-alpha blockade prevents neutrophil CD18 receptor upregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation. J. Clin Invest. 91, 1459–1468.

    Article  PubMed  CAS  Google Scholar 

  54. Han, J., Thompson, P., and Beutler, B. (1990) Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway. J. Exp. Med. 172, 391–394.

    Article  PubMed  CAS  Google Scholar 

  55. Endres, S., Fulle, H. J., Sinha, B., Stoll, D., Dinarello, C. A., Gerzer, R., et al. (1991) Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-alpha and interleukin-1 beta by human mononuclear cells. Immunology 72, 56–60.

    PubMed  CAS  Google Scholar 

  56. Kern, J. A., Lamb, R. J., Reed, J. C., Daniele, R. P., and Nowell, P. C. (1988) Dexamethasone inhibition of interleukin 1 beta production by human monocytes. Posttranscriptional mechanisms. J. Clin Invest. 81, 237–244.

    Article  PubMed  CAS  Google Scholar 

  57. Sano, H., Sudo, T., Yokode, M., Murayama, T., Kataoka, H., Takakura, N., et al. (2001) Functional blockade of platelet-derived growth factor receptor-beta but not of receptor-alpha prevents vascular smooth muscle cell accumulation in fibrous cap lesions in apolipoprotein E-deficient mice. Circulation 103, 2955–2960.

    PubMed  CAS  Google Scholar 

  58. Nicolosi, R. J., Wilson, T. A., and Krause, B. R. (1998) The ACAT inhibitor, CI-1011 is effective in the prevention and regression of aortic fatty streak area in hamsters. Atherosclerosis 137, 77–85.

    Article  PubMed  CAS  Google Scholar 

  59. Sasahara, M., Raines, E. W., Chait, A., Carew, T. E., Steinberg, D., Wahl, et al. (1994) Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol. I. Is the extent of atherosclerosis related to resistance of LDL to oxidation? J. Clin Invest. 94, 155–164.

    Article  PubMed  CAS  Google Scholar 

  60. Verlangieri, A. J. and Bush, M. J. (1992) Effects of d-alpha-tocopherol supplementation on experimentally induced primate atherosclerosis. J. Am. Coll. Nutr. 11, 131–138.

    PubMed  CAS  Google Scholar 

  61. Ikonomidis, I., Andreotti, F., Economou, E., Stefanadis, C., Toutouzas, P., and Nihoyannopoulos, P. (1999) Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 100, 793–798.

    PubMed  CAS  Google Scholar 

  62. Ridker, P. M., Rifai, N., Pfeffer, M. A., Sacks, F., and Braunwald, E. (1999) Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 100, 230–235.

    PubMed  CAS  Google Scholar 

  63. Bellosta, S., Bernini, F., Ferri, N, Quarato, P., Canavesi, M., Arnaboldi, L., et al. (1998) Direct vascular effects of HMG-CoA reductase inhibitors. Atherosclerosis 137(Suppl), S101–S109.

    Article  PubMed  CAS  Google Scholar 

  64. Lacoste, L., Lam, J. Y., Hung, J., Letchacovski, G., Solymoss, C. B., and Waters, D. (1995) Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation 92, 3172–3177.

    PubMed  CAS  Google Scholar 

  65. Ridker, P. M., Rifai, N., Pfeffer, M. A., Sacks, F. M., Moye, L. A., Goldman, S., et al. (1998) Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 98, 839–844.

    PubMed  CAS  Google Scholar 

  66. Kleinveld, H. A., Demacker, P. N., De Haan, A. F., and Stalenhoef, A. F. (1993) Decreased in vitro oxidizability of low-density lipoprotein in hypercholesterolaemic patients treated with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors. Eur J. Clin Invest. 23, 289–295.

    Article  PubMed  CAS  Google Scholar 

  67. Gwechenberger, M., Mendoza, L. H., Youker, K. A., Frangogiannis, N. G., Smith, C. W., Michael, L. H., et al. (1999) Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions. Circulation 99, 546–551.

    PubMed  CAS  Google Scholar 

  68. Irwin, M. W., Mak, S., Mann, D. L., Qu, R., Penninger, J. M., Yan, A., et al. (1999) Tissue expression and immunolocalization of tumor necrosis factor-alpha in postinfarction dysfunctional myocardium. Circulation 99, 1492–1498.

    PubMed  CAS  Google Scholar 

  69. Entman, M. L., Youker, K., Shappell, S. B., Siegel, C., Rothlein, R., Dreyer, W. J., et al. (1990) Neutrophil adherence to isolated adult canine myocytes: Evidence for a CD18-dependent mechanism. J. Clin Invest. 85, 1497–1506.

    Article  PubMed  CAS  Google Scholar 

  70. Smith, C. W., Entman, M. L., Lane, C. L., Beaudet, A. L., Ty, T. I., Youker, K., et al. (1991) Adherence of neutrophils to canine cardiac myocytes in vitro is dependent on intercellular adhesion molecule-1. J. Clin Invest. 88, 1216–1223.

    Article  PubMed  CAS  Google Scholar 

  71. Das, U. N., Padma, M., Sagar, P. S., Ramesh, G., and Koratkar, R. (1990) Stimulation of free radical generation in human leukocytes by various agents including tumor necrosis factor is a calmodulin dependent process. Biochem. Biophys. Res. Commun. 167, 1030–1036.

    Article  PubMed  CAS  Google Scholar 

  72. Aoki, N., Siegfried, M., and Lefer, A. M. (1989) Anti-EDRF effect of tumor necrosis factor in isolated, perfused cat carotid arteries. Am. J. Physiol. 256, H1509–H1512.

    PubMed  CAS  Google Scholar 

  73. Lefer, A. M. and Aoki, N. (1990) Leukocyte-dependent and leukocyte-independent mechanisms of impairment of endothelium-mediated vasodilation. Blood Vessels 27, 162–168.

    PubMed  CAS  Google Scholar 

  74. Cain, B. S., Harken, A. H., and Meldrum, D. R. (1999) Therapeutic strategies to reduce TNF-alpha mediated cardiac contractile depression following ischemia and reperfusion. J. Mol. Cell Cardiol. 31, 931–947.

    Article  PubMed  CAS  Google Scholar 

  75. Gumina, R. J., Schultz, J., Yao, Z., Kenny, D., Warltier, D. C., Newman, P. J., et al. (1996) Antibody to platelet/endothelial cell adhesion molecule-1 reduces myocardial infarct size in a rat model of ischemia-reperfusion injury. Circulation 94, 3327–3333.

    PubMed  CAS  Google Scholar 

  76. Jones, S. P., Trocha, S. D., Strange, M. B., Granger, D. N., Kevil, C. G., Bullard, D. C., et al. (2000) Leukocyte and endothelial cell adhesion molecules in a chronic murine model of myocardial reperfusion injury. Am. J. Physiol. 279, H2196–H2201.

    CAS  Google Scholar 

  77. Lucchesi, B. R. (1990) Modulation of leukocyte-mediated myocardial reperfusion injury. Ann. Rev. Physiol. 52, 561–576.

    Article  CAS  Google Scholar 

  78. Ferrer-Lopez, P., Renesto, P., Schattner, M., Bassot, S., Laurent, P., and Chignard, M. (1990) Activation of human platelets by C5a-stimulated neutrophils: A role for cathepsin G. Am. J. Physiol. 258, C1100–C1107.

    Google Scholar 

  79. Suzuku, M., Asako, H., Kubes, P., Jennings, S., Grisham, M. B., and Granger, D. N. Neutrophil-derived oxidants promote leukocyte adherence in postcapillary venules. Microvasc. Res. 42, 125–138.

    Google Scholar 

  80. Borgeat, P. and Samuelsson, B. Metabolism of arachidonic acid in polymorphonuclear leukocytes. Structural analysis of novel hydroxylated compounds. J. Biol. Chem. 254, 7865–7869.

    Google Scholar 

  81. Lotner, G. Z., Lynch, J. M., Betz, S. J., and Henson, P. M. (1980) Human neutrophil-derived platelet activating factor. J. Immunol. 124, 676–684.

    PubMed  CAS  Google Scholar 

  82. Montrucchio, G., Alloatti, G., Tetta, C., De Luca, R., Saunders, R. N., Emanuelli,G., Camussi, G. (1989) Release of platelet-activating factor from ischemic-reperfused rabbit heart. Am. J. Physiol. 256, H1236–H1246.

    PubMed  CAS  Google Scholar 

  83. Boyle, E. M., Jr., Canty, T. G., Jr., Morgan, E. N., Yun, W., Pohlman, T. H., and Verrier, E. D. (1999) Treating myocardial ischemia-reperfusion injury by targeting endothelial cell transcription. Ann. Thorac. Surg. 68, 1949–1953.

    Article  PubMed  Google Scholar 

  84. Fridovich, I. (1983) Superoxide radical: An endogenous toxicant. Annu. Rev. Pharmacol. Toxicol. 23, 239–257.

    Article  PubMed  CAS  Google Scholar 

  85. McCord, J. M., Fridovich, I. (1978) The biology and pathology of oxygen radicals. Ann. Intern. Med. 89, 122–127.

    PubMed  CAS  Google Scholar 

  86. Chandrasekar, B., Colston, J. T., Geimer, J., Cortez, D., and Freeman, G. L. (2000) Induction of nuclear factor kappaB but not kappaB-responsive cytokine expression during myocardial reperfusion injury after neutropenia. Free Rad. Biol. Med. 28, 1579–1588.

    Article  PubMed  CAS  Google Scholar 

  87. Collins, T., Read, M. A., Neish, A. S., Whitley, M. Z., Thanos, D, and Maniatis, T. (1995) Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J. 9, 899–909.

    PubMed  CAS  Google Scholar 

  88. Del Maestro, R. F. (1980) An approach to free radicals in medicine and biology. Acta Physiol. Scand. Suppl. 492, 153–168.

    PubMed  Google Scholar 

  89. McCord, J. M. (1985) Oxygen-derived free radicals in postischemic tissue injury. N. Engl. J. Med. 312, 159–163.

    Article  PubMed  CAS  Google Scholar 

  90. Ferrari, R., Ceconi, C., Curello, S., Guarnieri, C., Caldarera, C. M., Albertini, A., Visioli, O. (1985) Oxygen-mediated myocardial damage during ischaemia and reperfusion: role of the cellular defences against oxygen toxicity. J. Mol. Cell. Cardiol. 17, 937–945.

    Article  PubMed  CAS  Google Scholar 

  91. Guarnieri, C., Flamigni, F., and Caldarera, C. M. (1980) Role of oxygen in the cellular damage induced by re-oxygenation of hypoxic heart. J. Mol. Cell. Cardiol. 12, 797–808.

    Article  PubMed  CAS  Google Scholar 

  92. Kako, K. J. (1987) Free radical effects on membrane protein in myocardial ischemia/reperfusion injury. J. Mol. Cell. Cardiol. 19, 209–211.

    Article  PubMed  CAS  Google Scholar 

  93. Ohto, H., Maeda, H., Shibata, Y., Chen, R. F., Ozaki, Y., Higashihara, M., et al. (1985) A novel leukocyte differentiation antigen: Two monoclonal antibodies TM2 and TM3 define a 120-kd molecule present on neutrophils, monocytes, platelets, and activated lymphoblasts. Blood 66, 873–881.

    PubMed  CAS  Google Scholar 

  94. Ma, X. L., Lefer, D. J., Lefer, A. M., and Rothlein, R. (1992) Coronary endothelial and cardiac protective effects of a monoclonal antibody to intercellular adhesion molecule-1 in myocardial ischemia and reperfusion. Circulation 86, 937–946.

    PubMed  CAS  Google Scholar 

  95. Zhao, Z. Q., Lefer, D. J., Sato, H., Hart, K. K., Jefforda, P. R., and Vinten-Johansen, J. (1997) Monoclonal antibody to ICAM-1 preserves postischemic blood flow and reduces infarct size after ischemia-reperfusion in rabbit. J. Leuk. Biol. 62, 292–300.

    CAS  Google Scholar 

  96. Arai, M., Lefer, D. J., So, T., DiPaula, A, Aversano, T., and Becker, L. C. (1996) An anti-CD18 antibody limits infarct size and preserves left ventricular function in dogs with ischemia and 48-hour reperfusion. J. Am. Coll. Cardiol. 27, 1278–1285.

    Article  PubMed  CAS  Google Scholar 

  97. Aversano, T., Zhou, W., Nedelman, M., Nakada, M., and Weisman, H. (1995) A chimeric IgG4 monoclonal antibody directed against CD18 reduces infarct size in a primate model of myocardial ischemia and reperfusion. J. Am. Coll. Cardiol. 25, 781–788.

    Article  PubMed  CAS  Google Scholar 

  98. Lefer, D. J. (2000) Pharmacology of selectin inhibitors in ischemia/reperfusion states. Annu. Rev. Pharmacol. Toxicol. 40, 283–294.

    Article  PubMed  CAS  Google Scholar 

  99. Hoffmeyer, M. R., Scalia, R., Ross, C. R., Jones, S. P., and Lefer, D. J. (2000) PR-39, a potent neutrophil inhibitor, attenuates myocardial ischemia-reperfusion injury in mice. Am. J. Physiol. 279, H2824–H2828.

    CAS  Google Scholar 

  100. Altavilla, D., Deodato, B., Campo, G. M., Arlotta, M., Miano, M., Squadrito, G., et al. (2000) IRFI 042, a novel dual vitamin E-like antioxidant, inhibits activation of nuclear factor-kappaB and reduces the inflammatory response in myocardial ischemiareperfusion injury. Cardiovasc. Res. 47, 515–528.

    Article  PubMed  CAS  Google Scholar 

  101. Sakaguchi, T., Sawa, Y., Fukushima, N., Nishimura, M., Ichikawa, H., Kaneda, Y., Matsuda, H. (2001) A novel strategy of decoy transfection against nuclear factor-kappaB in myocardial preservation. Ann. Thorac. Surg. 71, 624–629.

    Article  PubMed  CAS  Google Scholar 

  102. Burke, S. E., Wright, C. D., Potoczak, R. E., Boucher, D. M., Dodd, G. D., Taylor, D. G., Jr., Kaplan, H. R. (1992) Reduction of canine myocardial infarct size by CI-959, an inhibitor of inflammatory cell activation. J. Cardiovasc. Pharmacol. 20, 619–629.

    Article  PubMed  CAS  Google Scholar 

  103. Gallagher, K. P., Buda, A. J., Pace, D., Gerren, R. A., and Shlafer, M. (1986) Failure of superoxide dismutase and catalase to alter size of infarction in conscious dogs after 3 hours of occlusion followed by reperfusion. Circulation 73, 1065–1076.

    PubMed  CAS  Google Scholar 

  104. Jolly, S. R., Kane, W. J., Bailie, M. B., Abrams, G. D., and Lucchesi, B. R. (1984) Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase. Circ. Res. 54, 277–285.

    PubMed  CAS  Google Scholar 

  105. Werns, S. W., Shea, M. J., Driscoll, E. M., Cohen, C., Abrams, G. D., Pitt, B., Lucchesi, B. R. (1985) The independent effects of oxygen radical scavengers on canine infarct size. Reduction by superoxide dismutase but not catalase. Circ. Res. 56, 895–898.

    PubMed  CAS  Google Scholar 

  106. Jones, S. P., Hoffmeyer, M. R., Sharp, B. R., Ho, Y. S., and Lefer, D. J. (2003) Role of intracellular antioxidant enzymes after in vivo myocardial ischemia and reperfusion. Am. J. Physiol. Heart Circ. Physiol. 284, H277–H282.

    PubMed  CAS  Google Scholar 

  107. Engler, R. and Gilpin, E. (1989) Can superoxide dismutase alter myocardial infarct size? Circulation 79, 1137–1142.

    PubMed  CAS  Google Scholar 

  108. Reimer, K. A. and Jennings, R. B. (1985) Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusion in dogs. Circulation 71, 1069–1075.

    PubMed  CAS  Google Scholar 

  109. Werns, S. W., Shea, M. J., Mitsos, S. E., Dysko, R. C., Fantone, J. C., Schork, M. A., et al. (1986) Reduction of the size of infarction by allopurinol in the ischemic-reperfused canine heart. Circulation 73, 518–524.

    PubMed  CAS  Google Scholar 

  110. Puett, D. W., Forman, M. B., Cates, C. U., Wilson, B. H., Hande, K. R., Friesinger, G. C., Virmani, R. (1987) Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion. Circulation 76, 678–686.

    PubMed  CAS  Google Scholar 

  111. Virmani, R, Fink, L. M., Gunter, K., and English, D. (1984) Effect of perfluorochemical blood substitutes on human neutrophil function. Transfusion 24, 343–347.

    Article  PubMed  CAS  Google Scholar 

  112. Bajaj, A. K., Cobb, M. A., Virmani, R., Gay, J. C., Light, R. T., and Forman, M. B. (1989) Limitation of myocardial reperfusion injury by intravenous perfluorochemicals. Role of neutrophil activation. Circulation 79, 645–656.

    PubMed  CAS  Google Scholar 

  113. Berne, R. M. (1980) The role of adenosine in the regulation of coronary blood flow. Circ. Res. 47, 807–813.

    PubMed  CAS  Google Scholar 

  114. Cronstein, B. N., Levin, R. I., Belanoff, J., Weissmann, G., and Hirschhorn, R. (1986) Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells. J. Clin Invest. 78, 760–770.

    Article  PubMed  CAS  Google Scholar 

  115. Tanabe, M., Terashita, Z., Nishikawa, K., and Hirata, M. (1984) Inhibition of coronary circulatory failure and thromboxane A2 release during coronary occlusion and reperfusion by 2-phenylaminoadenosine (CV-1808) in anesthetized dogs. J. Cardiovasc. Pharmacol. 6, 442–448.

    Article  PubMed  CAS  Google Scholar 

  116. Ross, R., Raines, E. W., and Bowen-Pope, D. F. (1986) The biology of platelet-derived growth factor. Cell 46, 155–169.

    Article  PubMed  CAS  Google Scholar 

  117. Ferrell, M., Fuster, V., Gold, H. K., and Chesebro, J. H. (1992) A dilemma for the 1990s. Choosing appropriate experimental animal model for the prevention of restenosis. Circulation 85, 1630–1631.

    PubMed  CAS  Google Scholar 

  118. Nobuyoshi, M., Kimura, T., Ohishi, H., Horiuchi, H., Nosaka, H., Hamasaki, N., et al. (1991) Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients. J. Am. Coll. Cardiol. 17, 433–439.

    Article  PubMed  CAS  Google Scholar 

  119. Harker, L. A. (1987) Role of platelets and thrombosis in mechanisms of acute occlusion and restenosis after angioplasty. Am. J. Cardiol. 60, 20B–28B.

    Article  PubMed  CAS  Google Scholar 

  120. Pober, J. S. (1988) Warner-Lambert/Parke-Davis award lecture. Cytokine-mediated activation of vascular endothelium. Physiology and pathology. Am. J. Pathol. 133, 426–433.

    PubMed  CAS  Google Scholar 

  121. Mantovani, A. and Dejana, E. (1989) Cytokines as communication signals between leukocytes and endothelial cells. Immunol. Today 10, 370–375.

    Article  PubMed  CAS  Google Scholar 

  122. Paleolog, E. M., Crossman, D. C., McVey, J. H., and Pearson, J. D. (1990) Differential regulation by cytokines of constitutive and stimulated secretion of von Willebrand factor from endothelial cells. Blood 75, 688–695.

    PubMed  CAS  Google Scholar 

  123. Springer, T. A. (1994) Traffic signals for lymphocyte re-Circulation and leukocyte emigration: The multi-step paradigm. Cell 76, 301–314.

    Article  PubMed  CAS  Google Scholar 

  124. Baumgartner, H. R., and Muggli, R. Adhesion and aggregation: morphological demonstration and quantification in vivo and in vitro, in Platelets in Biology and Pathology (Gordon, J. L., ed.), Elsevier Press Inc, Amsterdam, 1976, pp. 23–39.

    Google Scholar 

  125. Walker, L. N., Bowen-Pope, D. F., Ross, R., and Reidy, M. A. (1986) Production of platelet-derived growth factor-like molecules by cultured arterial smooth muscle cells accompanies proliferation after arterial injury. Proc. Natl. Acad. Sci. USA 83, 7311–7315.

    Article  PubMed  CAS  Google Scholar 

  126. Antiplatelet Trialists’ Collaboration. (1994) Collaborative overview of randomised trials of antiplatelet therapy-I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Br. Med. J. 308, 81–106.

    Google Scholar 

  127. Maresta, A., Balducelli, M., Cantini, L., Casari, A., Chioin, R., Fabbri, M., et al. (1994) Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, reduces restenosis after percutaneous transluminal coronary angioplasty. Results of the randomized, double-blind STARC study. Studio Trapidil versus Aspirin nella Restenosi Coronarica. Circulation 90, 2710–2715.

    PubMed  CAS  Google Scholar 

  128. Dosquet, C., Weill, D., and Wautier, J. L. (1995) Cytokines and thrombosis. J. Cardiovasc. Pharmacol. 25(Suppl 2), S13–S19.

    Article  PubMed  CAS  Google Scholar 

  129. Huang, J., Driscoll, E. M., Gonzales, M. L., Park, A. M., and Lucchesi, B. R. (2000) Prevention of arterial thrombosis by intravenously administered platelet P2T receptor antagonist AR-C69931MX in a canine model. J. Pharmacol. Exp. Ther. 295, 492–499.

    PubMed  CAS  Google Scholar 

  130. Shi, Y., Fard, A., Galeo, A., Hutchinson, H. G., Vermani, P., Dodge, G. R., et al. (1994) Transcatheter delivery of c-myc antisense oligomers reduces neointimal formation in a porcine model of coronary artery balloon injury. Circulation 90, 944–951.

    PubMed  CAS  Google Scholar 

  131. Palmer, R. M., Ashton, D. S., and Moncada, S. (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333, 664–666.

    Article  PubMed  CAS  Google Scholar 

  132. Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E., and Chaudhuri, G. (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc. Natl. Acad. Sci. USA 84, 9265–9269.

    Article  PubMed  CAS  Google Scholar 

  133. Chowienczyk, P. J., Watts, G. F., Cockcroft, J. R., and Ritter, J. M. (1992) Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolaemia. Lancet 340, 1430–1432.

    Article  PubMed  CAS  Google Scholar 

  134. Creager, M. A., Cooke, J. P., Mendelsohn, M. E., Gallagher, S. J., Coleman, S. M., Loscalzo, J., et al. (1990) Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J. Clin Invest. 86, 228–234.

    Article  PubMed  CAS  Google Scholar 

  135. Rubanyi, G. M. (1988) Vascular effects of oxygen-derived free radicals. Free Rad. Biol. Med. 4, 107–120.

    Article  PubMed  CAS  Google Scholar 

  136. Chu, A., Chambers, D. E., Lin, C. C., Kuehl, W. D., Palmer, R. M., Moncada, S., et al. (1991) Effects of inhibition of nitric oxide formation on basal vasomotion and endothelium-dependent responses of the coronary arteries in awake dogs. J. Clin Invest. 87, 1964–1968.

    Article  PubMed  CAS  Google Scholar 

  137. Kubes, P., Suzuki, M., and Granger, D. N. (1991) Nitric oxide: An endogenous modulator of leukocyte adhesion. Proc. Natl. Acad. Sci. USA 8, 4651–4655.

    Article  Google Scholar 

  138. Bassenge, E. (1991) Antiplatelet effects of endothelium-derived relaxing factor and nitric oxide donors. Eur. Heart J. 12(Suppl E), 12–15.

    PubMed  CAS  Google Scholar 

  139. Assender, J. W., Southgate, K. M., Hallett, M. B., and Newby, A. C. (1992) Inhibition of proliferation, but not of Ca2+ mobilization, by cyclic AMP and GMP in rabbit aortic smooth-muscle cells. Biochem. J. 288, 527–532.

    PubMed  CAS  Google Scholar 

  140. Jessup, W., Mohr, D., Gieseg, S. P., Dean, R. T., and Stocker, R. (1992) The participation of nitric oxide in cell. Biochim. Biophys. Acta. 1180, 73–82.

    PubMed  CAS  Google Scholar 

  141. Ohlstein, E. H. and Nichols, A. J. (1989) Rabbit polymorphonuclear neutrophils elicit endothelium-dependent contraction in vascular smooth muscle. Circ. Res. 65, 917–924.

    PubMed  CAS  Google Scholar 

  142. Lefer, D. J., Jones, S. P., Girod, W. G., Baines, A., Grisham, M. B., Cockrell, A. S., et al. (1999) Leukocyte-endothelial cell interactions in nitric oxide synthase-deficient mice. Am. J. Physiol. 276, H1943–H1950.

    PubMed  CAS  Google Scholar 

  143. Barrett, M. L., Willis, A. L., and Vane, J. R. (1989) Inhibition of platelet-derived mitogen release by nitric oxide (EDRF). Agents Actions 27, 488–491.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA

    Melanie B. Smith & David J. Lefer

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  1. Melanie B. Smith
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  2. David J. Lefer
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  1. Department of Pharmacology, Forest Research Institute, Jersey City, NJ

    Michael K. Pugsley

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Smith, M.B., Lefer, D.J. (2003). Development of Anti-Inflammatory Drugs for Cardiovascular Disease. In: Pugsley, M.K. (eds) Cardiac Drug Development Guide. Methods in Pharmacology and Toxicology. Humana Press. https://doi.org/10.1385/1-59259-404-2:87

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  • DOI: https://doi.org/10.1385/1-59259-404-2:87

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