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Inflammation in early atherogenesis: impact of ACE inhibition

R. De Caterina*,1,2 and C. Manes3

a "G. d'Annunzio" University, Chieti, Italy
b CNR Institute of Clinical Physiology, Pisa, Italy
c Institute of Cardiology, Bologna University, Italy

* Raffaele De Caterina, MD, PhD, Chair of Cardiology, "G. d'Annunzio" University - Chieti, c/o Ospedale S. Camillo de Lellis, Via Forlanini, 50, 66100 Chieti, Italy.

Abstract

Cytokines and other inflammatory mediators induce functional changes in the endothelium ("endothelium activation"), which have been shown to be markers of atherosclerotic vascular disease. Endothelial activation accompanies and promotes vascular disease, and is associated with overexpression of chemoattractants and adhesion molecules, which in turn lead to leukocyte binding to the endothelium. The nuclear factor-{kappa}B (NF-{kappa}B) system appears to regulate the expression of many of the genes involved in this process. Angiotensin II contributes to atherogenesis by increasing expression of many pro-inflammatory genes, in part by inducing oxidative stress, which activates NF-{kappa}B.

Key Words: ACE inhibitors • oxidative stress • inflammation

References

  1. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000;355:253–259[CrossRef][Web of Science][Medline]
  2. Kowala MC, Grove RI, Aberg G. Inhibitors of angiotensin converting enzyme decrease early atherosclerosis in hyperlipidemic hamsters: fosinopril reduces plasma cholesterol and captopril inhibits macrophage-foam cell accumulation independently of blood pressure and plasma lipids. Atherosclerosis. 1994;108:61–72[CrossRef][Web of Science][Medline]
  3. Hayek T, Attias J, Smith J, et al. Antiatherosclerotic and antioxidative effects of captopril in apolipoprotein E-deficient mice. J Cardiovasc Pharmacol. 1998;31:540–544[CrossRef][Web of Science][Medline]
  4. Keidar S, Attias J, Coleman R, Wirth K, Scholkens B, Hayek T. Attenuation of atherosclerosis in apolipoptotein E-deficient mice by ramipril is dissociated from its antihypertensive effect and from potentiation of bradykinin. J Cardiovasc Pharmacol. 2000;35:64–72[CrossRef][Web of Science][Medline]
  5. Candido R, Jandeleit-Dahm KA, Cao Z, et al. Prevention of accelerated atherosclerosis by angiotensin-converting enzyme inhibition in diabetic apolipoprotein E-deficient mice. Circulation. 2002;106:246–253[Abstract/Free Full Text]
  6. Schieffer B. Interaction of interleukin-6 and angiotensis II and atherosclerosis: culprit for inflammation. Eur Heart J. 2003;5(Suppl. A):A25–A30[CrossRef]
  7. Gimbrone MA Jr., Kume N, Cybulsky MI. Vascular endothelial dysfunction and the pathogenesis of atherosclerosis. Weber PC, Leaf A. Atherosclerosis Reviews. New York: Raven Press; 1993.
  8. Gimbrone MA Jr.. Vascular endothelium in health and disease. (Chapter 4) Haber E. Molecular Cardiovascolar Medicine. New York, NY: Scientific American Medicine; 1995.
  9. De Caterina R, Gimbrone MA Jr.. Leukocyte-endothelial interactions and the pathogenesis of atherosclerosis. Kristensen SD, Schmidt EB, De Caterina R, Endres S. n-3 Fatty Acids—Prevention and Treatment in Vascular Disease. London: Springer Verlag; 1995. p. 9–24
  10. Cybulsky MI, Gimbrone MA Jr.. Endothelial-leukocyte adhesion molecules in acute inflammation and atherogenesis. Simionescu N, Simionescu M. Endothelial cell dysfunctions. New York: Plenum Press; 1992. p. 129–140
  11. Cybulsky MI, Gimbrone MA Jr.. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991;251:788–791[Abstract/Free Full Text]
  12. Li H, Cybulsky MI, Gimbrone MA Jr., Libby P. An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscl Thromb. 1993;13:197–204[Abstract/Free Full Text]
  13. Cybulsky MI, Iiyama K, Li H, et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest. 2001;107:1255–1262[Web of Science][Medline]
  14. Gu L, Okada Y, Clinton SK, et al. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell. 1998;2:275–281[CrossRef][Web of Science][Medline]
  15. Rajavashisth T, Qiao JH, Tripathi S, et al. Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 1998;101:2702–2710[Web of Science][Medline]
  16. Kishimoto T, Taga T, Akira S. Cytokine signal transduction. Cell. 1994;76:253–262[CrossRef][Web of Science][Medline]
  17. Collins T. Endothelial nuclear factor-kappa B and the initiation of the atherosclerotic lesion. Lab Invest. 1993;68:499–508[Web of Science][Medline]
  18. Marui N, Offermann MK, Swerlick R, et al. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest. 1993;92:1866–1874
  19. Collins T, Read MA, Neish AS, Whitley MZ, Thanos D, Maniatis T. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J. 1995;9:899–909[Abstract]
  20. Clinton SK, Libby P. Cytokines and growth factors in atherogenesis. Arch Pathol Lab Med. 1992;116:1292–1300[Web of Science][Medline]
  21. Schwenke DC, Carew TE. Initiation of atherosclerotic lesions in cholesterol-fed rabbits. II. Selective retention of LDL vs. selective increases in LDL permeability in susceptible sites of arteries. Arteriosclerosis. 1989;9:908–918[Abstract/Free Full Text]
  22. Berliner JA, Navab M, Fogelman AM, et al. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation. 1995;91:2488–2496[Abstract/Free Full Text]
  23. Shih DM, Gu L, Hama S, et al. Genetic-dietary regulation of serum paraoxonase expression and its role in atherogenesis in a mouse model. J Clin Invest. 1996;97:1630–1639[Web of Science][Medline]
  24. Schmidt AM, Hori O, Chen JX, et al. Advanced glycation end-products interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes. J Clin Invest. 1995;96:1395–1403
  25. Basta G, Lazzerini G, Massaro M, et al. Advanced glycation end products activate endothelium through signal-transduction receptor RAGE: a mechanism for amplification of inflammatory responses. Circulation. 2002;105:816–822[Abstract/Free Full Text]
  26. Weiss D, Sorescu D, Taylor WR. Angiotensin II and atherosclerosis. Am J Cardiol. 2001;87:25C–32C[CrossRef][Web of Science][Medline]
  27. Tummala PE, Chen XL, Sundell CL, et al. Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: a potential link between the renin-angiotensin system and atherosclerosis. Circulation. 1999;100:1223–1229[Abstract/Free Full Text]
  28. Kranzhofer R, Schmidt J, Pfeiffer CA, Hagl S, Libby P, Kubler W. Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1999;19:1623–1629[Abstract/Free Full Text]
  29. Grafe M, Auch-Schwelk W, Zakrzewicz A, et al. Angiotensin II-induced leukocyte adhesion in human coronary endothelial cells is mediated by E-selectin. Circ Res. 1997;81:804–811[Abstract/Free Full Text]
  30. Kim JA, Berliner JA, Nadler JL. Angiotensin II increases monocyte binding to endothelial cells. Biochem Biophys Res Commun. 1996;226:862–868[CrossRef][Web of Science][Medline]
  31. Jilma B, Li-Saw-Hee FL, Wagner OF, Beevers DG, Lip GY. Effects of enalapril and losartan on circulating adhesion molecules and monocyte chemotactic protein-1. Clin Sci (Lond). 2002;103:131–136[Medline]
  32. Navalkar S, Parthasarathy S, Santanam N, Khan BV. Irbesartan, an angiotensin type 1 receptor inhibitor, regulates markers of inflammation in patients with premature atherosclerosis. J Am Coll Cardiol. 2001;37:440–444[Abstract/Free Full Text]
  33. Prasad A, Koh KK, Schenke WH, et al. Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis. Am Heart J. 2001;142:248–253[CrossRef][Web of Science][Medline]
  34. Furie B, Furie BC, Flaumenhaft R. A journey with platelet P-selectin: the molecular basis of granule secretion, signalling and cell adhesion. Thromb Haemost. 2001;86:214–221[Web of Science][Medline]
  35. Han Y, Runge MS, Brasier AR. Angiotensin II induces interleukin-6 transcription in vascular smooth muscle cells through pleiotropic activation of nuclear factor-kappa B transcription factors. Circ Res. 1999;84:695–703[Abstract/Free Full Text]
  36. Schieffer B, Schieffer E, Hilfiker-Kleiner D, et al. Expression of angiotensin II and interleukin 6 in human coronary atherosclerotic plaques: potential implications for inflammation and plaque instability. Circulation. 2000;101:1372–1378[Abstract/Free Full Text]
  37. Keidar S, Heinrich R, Kaplan M, Hayek T, Aviram M. Angiotensin II administration to atherosclerotic mice increases macrophage uptake of oxidized LDL: a possible role for inteleukin-6. Arterioscler Thromb Vasc Biol. 2001;21:1464–1469[Abstract/Free Full Text]
  38. Hernandez-Presa MA, Bustos C, Ortego M, et al. Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-kappa B activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis. Circulation. 1997;95:1532–1541[Abstract/Free Full Text]
  39. Chen X-L, Tummala PE, Olbrych MT, Alexander RW, Medford RM. Angiotensin II induces monocyte chemoattractant protein-1 gene expression in rat vascular smooth muscle cells. Circ Res. 1998;83:952–959[Abstract/Free Full Text]
  40. Chen H, Li D, Saldeen T, Phillips MI, Mehta JL. Attenuation of tissue P-selectin and MCP-1 expression and intimal proliferation by AT(1) receptor blockade in hyperlipidemic rabbits. Biochem Biophys Res Commun. 2001;282:474–479[CrossRef][Web of Science][Medline]
  41. Hernandez-Presa MA, Bustos C, Ortego M, Tunon J, Ortega L, Egido L. ACE inhibitor quinapril reduces the arterial expression of NF-kappaB-dependent proinflammatory factors but not of collagen I in a rabbit model of atherosclerosis. Am J Pathol. 1998;153:1825–1837[Abstract/Free Full Text]
  42. Chen H, Li D, Sawamura T, Inoue K, Mehta JL. Upregulation of LOX-1 expression in aorta of hypercholesterolemic rabbits: modulation by losartan. Biochem Biophys Res Commun. 2000;276:1100–1104[CrossRef][Web of Science][Medline]
  43. Chen H, Li D, Mehta JL. Modulation of matrix metalloproteinase-1, its tissue inhibitor and nuclear factor-kappa B by losartan in hypercholesterolemic rabbits. J Cardiovasc Pharmacol. 2002;39:332–339[CrossRef][Web of Science][Medline]
  44. Li J, Brasier AR. Angiotensinogen gene activation by angiotensin II is mediated by the rel A (nuclear factor-kappaB 65) transcription factor: one mechanism for the renin angiotensin system positive feedback loop in hepatocytes. Mol Endocrinol. 1996;10:252–264[Abstract/Free Full Text]
  45. Brasier AR, Jamaluddin M, Han Y, Patterson C, Runge MS. Angiotensin II induces gene transcription through cell-type-dependent effects on the nuclear factor-kappaB (NF-kappaB) transcription factor. Mol Cell Biochem. 2000;212:155–169[CrossRef][Web of Science][Medline]
  46. Brasier AR, Recinos A 3rd, Eledrisi MS. Vascular inflammation and the renin-angiotensin system. Arterioscler Thromb Vasc Biol. 2002;22:1257–1266[Abstract/Free Full Text]
  47. Kranzhofer R, Browatzki M, Schmidt J, Kubler W. Angiotensin II activates the proinflammatory transcription factor nuclear factor-kappaB in human monocytes. Biochem Biophys Res Commun. 1999;257:826–828[CrossRef][Web of Science][Medline]
  48. Nickenig G, Harrison DG. The AT(1)-type angiotensin receptor in oxidative stress and atherogenesis: part I: oxidative stress and atherogenesis. Circulation. 2002;105:393–396[Free Full Text]
  49. Nickenig G, Harrison DG. The AT(1)-type angiotensin receptor in oxidative stress and atherogenesis: Part II: AT(1) receptor regulation. Circulation. 2002;105:530–536[Free Full Text]
  50. Landmesser U, Drexler H. Oxidative stress, the renin-angiotensin system, and atherosclerosis. Eur Heart J. 2003;5(Supp. A):A3–A7[CrossRef]
  51. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulated NADH and NADPH activity in cultured vascular smooth muscle cells. Circ Res. 1994;74:1141–1148[Abstract/Free Full Text]
  52. Griendling K, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res. 2000;86:494–501[Abstract/Free Full Text]
  53. Meyer JW, Schmitt ME. A central role for the endothelial NDPH oxidase in atherosclerosis. FEBS Lett. 2000;472:1–4[CrossRef][Web of Science][Medline]
  54. Mollnau H, Wendt M, Szocs K, et al. Effects of angiotensin II infusion on the expression and function of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ Res. 2002;90:E58–E65
  55. Griendling K, Sorescu D, Lassegue B, Ushio-Fukai M. Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol. 2000;20:2175–2183[Abstract/Free Full Text]
  56. Wassmann S, Laufs U, Baumer AT, et al. Inhibition of geranyl-geranylation reduces angiotensin II-mediated free radical production in vascular smooth muscle cells: involvement of angiotensin AT1 receptor expression and Rac1 GTPase. Mol Pharmacol. 2001;59:646–654[Abstract/Free Full Text]
  57. Wang W, Wang S, Yan L, et al. Superoxide production and reactive oxygen species signaling by endothelial nitric-oxide synthase. J Biol Chem. 2000;275:16899–16903[Abstract/Free Full Text]
  58. Hink U, Li H, Mollnau H, et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res. 2001;88:e14–e22
  59. Pueyo ME, Gonzalez W, Nicoletti A, Savoie F, Arnal JF, Michel JB. Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress. Arterioscler Thromb Vasc Biol. 2000;20:645–651[Abstract/Free Full Text]
  60. De Caterina R, Libby P, Peng H-B, et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest. 1995;96:60–68
  61. Armstead VE, Minchenko AG, Schuhl RA, Hayward R, Nossuli TO, Lefu AM. Regulation of P-selectin expression in human endothelial cells by nitric oxide. Am J Physiol. 1997;273:H740–H746
  62. Huie RE, Padmaja S. Reaction of no with superoxide. Free Radic Res Commun. 1993;18:195–199[Web of Science][Medline]
  63. Landmesser U, Harrison DG. Oxidant stress as a marker for cardiovascular events: Ox marks the spot. Circulation. 2001;104:2638–2640[Free Full Text]
  64. Münzel T, Harrison DG. Increased superoxide in heart failure: a biochemical baroreflex gone awry. Circulation. 1999;100:216–218[Free Full Text]
  65. De Caterina R, Cybulsky MI, Clinton SK, Gimbrone MA Jr, Libby P. The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arterioscl Thromb. 1994;14:1829–1836[Abstract/Free Full Text]
  66. De Caterina R, Libby P. Control of endothelial leukocyte adhesion molecules by fatty acids. Lipids. 1996;31(Suppl. 1):S557–S563
  67. Carluccio MA, Massaro M, Bonfrate C, et al. Oleic acid inhibits endothelial activation: a direct vascular antiatherogenic mechanisms of a nutritional component in the mediterranean diet. Arterioscler Thromb Vasc Biol. 1999;19:220–228[Abstract/Free Full Text]
  68. Cooke JP, Singer AH, Tsao P, Zera P, Rowan RA, Billingham ME. Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit. J Clin Invest. 1992;90:1168–1172
  69. Simoncini T, De Caterina R, Genazzani AR. Selective estrogen receptor modulators: different actions on vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells. J Clin Endocrinol Metab. 1999;84:815–818[Abstract/Free Full Text]
  70. Simoncini T, Maffei S, Basta G, et al. Estrogens and glucocorticoids inhibit endothelial vascular cell adhesion molecule-1 expression by different transcriptional mechanisms. Circ Res. 2000;87:19–25[Abstract/Free Full Text]
  71. Zampolli a, Basta G, Lazzerini G, Feelisch M, De Caterina R. Inhibition of endothelial cell activation by nitric oxide donors. J Pharmacol Exp Ther. 2000;295:818–823[Abstract/Free Full Text]
  72. Vaughan D. Pharmacology of ACE inhibitorss versus AT1 blockers. Can J Cardiol. 2000;16(Suppl. E):36E–40E
  73. Peng H-B, Libby P, Liao J. Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B. J Biol Chem. 1995;270:14214–14219[Abstract/Free Full Text]
  74. Gohlke P, Pees C, Unger T. AT2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism. Hypertension. 1998;31:349–355[Abstract/Free Full Text]
  75. Searles CD, Harrison DG. The interaction of nitric oxide, bradykinin, and the angiotensin II type 2 receptor: lessons learned from transgenic mice. J Clin Invest. 1999;104:1013–1014[Web of Science][Medline]
  76. Schuh JR, Blehm DJ, Frierdich GE, McMahon EG, Blaine EH. Differential effects of renin-angiotensin system blockade on atherogenesis in cholesterol-fed rabbits. J Clin Invest. 1993;91:1453–1458
  77. Fennessy PA, Campbell JH, Mendelsohn FAO, Campbell GR. Angiotensin-converting enzyme inhibitors and atherosclerosis: relevance of animal models to human disease. Clin Exp Pharmacol Physiol. 1996;23(8):S30–S32[Web of Science][Medline]
  78. Murphey L, Vaughan D, Brown N. Contribution of bradykinin to the cardioprotective efforts of ACE inhibition. Eur Heart J. 2003;5(Suppl. A):A37–A41[CrossRef]
  79. Harrison DG, Ohara Y. Physiologic consequences of increased vascular oxidant stresses in hypercholesterolemia and atherosclerosis: implications for impaired vasomotion. Am J Cardiol. 1995;75:75B–81B[CrossRef][Medline]
  80. Huraux C, Makita T, Kurz S, et al. Superoxide production, risk factors, and endothelium-dependent relaxations in human internal mammary arteries. Circulation. 1999;99:53–59[Abstract/Free Full Text]

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