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Cardiology Research and Practice
Volume 2011, Article ID 714515, 10 pages
http://dx.doi.org/10.4061/2011/714515
Review Article

Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

1Department of Gastroenterology, Turkiye Yuksek Ihtisas Teaching and Research Hospital, 06100 Ankara, Turkey
2Department of Gastroenterology, Ankara Numune Education and Research Hospital, 06100 Ankara, Turkey
3Department of Internal Medicine, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey

Received 28 September 2010; Revised 14 October 2010; Accepted 23 October 2010

Academic Editor: Masaki Mogi

Copyright © 2011 Yavuz Beyazit et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. M. Ferrario and W. B. Strawn, “Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease,” American Journal of Cardiology, vol. 98, no. 1, pp. 121–128, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. S. Oparil and E. Haber, “The renin-angiotensin system (first of two parts),” New England Journal of Medicine, vol. 291, no. 9, pp. 389–401, 1974. View at Google Scholar
  3. S. Oparil and E. Haber, “The renin angiotensin system (Second of two parts),” New England Journal of Medicine, vol. 291, no. 9, pp. 446–457, 1974. View at Google Scholar · View at Scopus
  4. M. Paul, A. P. Mehr, and R. Kreutz, “Physiology of local renin-angiotensin systems,” Physiological Reviews, vol. 86, no. 3, pp. 747–803, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. M. de Gasparo, K. J. Catt, T. Inagami, J. W. Wright, and TH. Unger, “International union of pharmacology. XXIII. The angiotensin II receptors,” Pharmacological Reviews, vol. 52, no. 3, pp. 415–472, 2000. View at Google Scholar · View at Scopus
  6. V. J. Dzau, “Tissue angiotensin and pathobiology of vascular disease a unifying hypothesis,” Hypertension, vol. 37, no. 4, pp. 1047–1052, 2001. View at Google Scholar
  7. M. Ruiz-Ortega, O. Lorenzo, M. Rupérez et al., “Role of the renin-angiotensin system in vascular diseases: expanding the field,” Hypertension, vol. 38, no. 6, pp. 1382–1387, 2001. View at Google Scholar · View at Scopus
  8. V. J. Dzau and R. Re, “Tissue angiotensin system in cardiovascular medicine: a paradigm shift?” Circulation, vol. 89, no. 1, pp. 493–498, 1994. View at Google Scholar · View at Scopus
  9. J. N. Cohn and G. Tognoni, “A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure,” New England Journal of Medicine, vol. 345, no. 23, pp. 1667–1675, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. R. A. Lafayette, G. Mayer, S. K. Park, and T. W. Meyer, “Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass,” Journal of Clinical Investigation, vol. 90, no. 3, pp. 766–771, 1992. View at Google Scholar · View at Scopus
  11. H. Yamagishi, S. Kim, T. Nishikimi, K. Takeuchi, and T. Takeda, “Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats,” Journal of Molecular and Cellular Cardiology, vol. 25, no. 11, pp. 1369–1380, 1993. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. H. F. Cheng, B. N. Becker, K. D. Burns, and R. C. Harris, “Angiotensin II upregulates type-1 angiotensin II receptors in renal proximal tubule,” Journal of Clinical Investigation, vol. 95, no. 5, pp. 2012–2019, 1995. View at Google Scholar · View at Scopus
  13. R. H. Yang, H. Jin, J. M. Wyss, and S. Oparil, “Depressor effect of blocking angiotensin subtype 1 receptors in anterior hypothalamus,” Hypertension, vol. 19, no. 5, pp. 475–481, 1992. View at Google Scholar · View at Scopus
  14. M. I. Phillips and C. Sumners, “Angiotensin II in central nervous system physiology,” Regulatory Peptides, vol. 78, no. 1–3, pp. 1–11, 1998. View at Publisher · View at Google Scholar · View at Scopus
  15. K. Arakawa and H. Urata, “Hypothesis regarding the pathophysiological role of alternative pathways of angiotensin II formation in atherosclerosis,” Hypertension, vol. 36, no. 4, pp. 638–641, 2000. View at Google Scholar · View at Scopus
  16. H. Urata, H. Nishimura, and D. Ganten, “Chymase-dependent angiotensin II forming system in humans,” American Journal of Hypertension, vol. 9, no. 3, pp. 277–284, 1996. View at Publisher · View at Google Scholar · View at Scopus
  17. H. Urata, A. Kinoshita, D. M. Perez et al., “Cloning of the gene and cDNA for human heart chymase,” Journal of Biological Chemistry, vol. 266, no. 26, pp. 17173–17179, 1991. View at Google Scholar · View at Scopus
  18. A. Wolny, J. P. Clozel, J. Rein et al., “Functional and biochemical analysis of angiotensin II-forming pathways in the human heart,” Circulation Research, vol. 80, no. 2, pp. 219–227, 1997. View at Google Scholar · View at Scopus
  19. I. C. Haznedaroglu, S. Tuncer, and M. Gursoy, “A local renin-angiotensin system in the bone marrow,” Medical Hypotheses, vol. 46, no. 6, pp. 507–510, 1996. View at Publisher · View at Google Scholar · View at Scopus
  20. H. Kato, J. Ishida, S. Imagawa et al., “Enhanced erythropoiesis mediated by activation of the renin-angiotensin system via angiotensin II type 1a receptor,” FASEB Journal, vol. 19, no. 14, pp. 2023–2025, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. D. Fukuda and M. Sata, “Role of bone marrow renin-angiotensin system in the pathogenesis of atherosclerosis,” Pharmacology and Therapeutics, vol. 118, no. 2, pp. 268–276, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. M. Hernández-Presa, C. Bustos, M. Ortego et al., “Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-κB activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis,” Circulation, vol. 95, no. 6, pp. 1532–1541, 1997. View at Google Scholar · View at Scopus
  23. L. Pastore, A. Tessitore, S. Martinotti et al., “Angiotensin II stimulates intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells and increases soluble ICAM-1 release in vivo,” Circulation, vol. 100, no. 15, pp. 1646–1652, 1999. View at Google Scholar · View at Scopus
  24. M. E. Pueyo, W. Gonzalez, A. Nicoletti, F. Savoie, J. F. Arnal, and J. B. Michel, “Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-κB activation induced by intracellular oxidative stress,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 3, pp. 645–651, 2000. View at Google Scholar · View at Scopus
  25. T. Petnehazy, K. Y. Stokes, K. C. Wood, J. Russell, and D. N. Granger, “Role of blood cell-associated AT1 receptors in the microvascular responses to hypercholesterolemia,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 2, pp. 313–318, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. M. Sata and D. Fukuda, “Crucial role of renin-angiotensin system in the pathogenesis of atherosclerosis,” Journal of Medical Investigation, vol. 57, no. 1-2, pp. 12–25, 2010. View at Google Scholar · View at Scopus
  27. N. Iwai and T. Inagami, “Identification of two subtypes in the rat type I angiotensin II receptor,” FEBS Letters, vol. 298, no. 2-3, pp. 257–260, 1992. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Nouet and C. Nahmias, “Signal transduction from the angiotensin II AT receptor,” Trends in Endocrinology and Metabolism, vol. 11, no. 1, pp. 1–6, 2000. View at Publisher · View at Google Scholar · View at Scopus
  29. P. P. Sayeski and K. E. Bernstein, “Signal transduction mechanisms of the angiotensin II type AT-receptor: looking beyond the heterotrimeric G protein paradigm,” Journal of the Renin-Angiotensin-Aldosterone System, vol. 2, no. 1, pp. 4–10, 2001. View at Google Scholar · View at Scopus
  30. B. C. Yang, M. I. Phillips, D. Mohuczy et al., “Increased angiotensin II type 1 receptor expression in hypercholesterolemic atherosclerosis in rabbits,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 18, no. 9, pp. 1433–1439, 1998. View at Google Scholar · View at Scopus
  31. Z. Q. Wang, A. F. Moore, R. Ozono, H. M. Siragy, and R. M. Carey, “Immunolocalization of subtype 2 angiotensin II (AT) receptor protein in rat heart,” Hypertension, vol. 32, no. 1, pp. 78–83, 1998. View at Google Scholar · View at Scopus
  32. G. H. Gibbons and V. J. Dzau, “The emerging concept of vascular remodeling,” New England Journal of Medicine, vol. 330, no. 20, pp. 1431–1438, 1994. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. K. A. Robinson, F. J. Candal, N. A. Scott, and E. W. Ades, “Seeding of vascular grafts with an immortalized human dermal microvascular endothelial cell line,” Angiology, vol. 46, no. 2, pp. 107–114, 1995. View at Google Scholar · View at Scopus
  34. S. Kinlay and P. Ganz, “Role of endothelial dysfunction in coronary artery disease and implications for therapy,” American Journal of Cardiology, vol. 80, no. 9, pp. 11I–16I, 1997. View at Google Scholar · View at Scopus
  35. P. Libby, G. Sukhova, R. T. Lee, and Z. S. Galis, “Cytokines regulate vascular functions related to stability of the atherosclerotic plaque,” Journal of Cardiovascular Pharmacology, vol. 25, supplement 2, pp. S9–S12, 1995. View at Google Scholar · View at Scopus
  36. J. M. Neutel, “Effect of the renin-angiotensin system on the vessel wall: using ACE inhibition to improve endothelial function,” Journal of Human Hypertension, vol. 18, no. 9, pp. 599–606, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. L. Gu, Y. Okada, S. K. Clinton et al., “Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice,” Molecular Cell, vol. 2, no. 2, pp. 275–281, 1998. View at Google Scholar · View at Scopus
  38. Y. Han, M. S. Runge, and A. R. Brasier, “Angiotensin II induces interleukin-6 transcription in vascular smooth muscle cells through pleiotropic activation of nuclear factor-κb transcription factors,” Circulation Research, vol. 84, no. 6, pp. 695–703, 1999. View at Google Scholar · View at Scopus
  39. A. R. Brasier, A. Recinos, M. S. Eledrisi, and M. S. Runge, “Vascular inflammation and the renin-angiotensin system,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 22, no. 8, pp. 1257–1266, 2002. View at Publisher · View at Google Scholar · View at Scopus
  40. B. Williams, A. Q. Baker, B. Gallacher, and D. Lodwick, “Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells,” Hypertension, vol. 25, no. 5, pp. 913–917, 1995. View at Google Scholar · View at Scopus
  41. C. Cheng, D. Tempel, R. Van Haperen et al., “Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress,” Circulation, vol. 113, no. 23, pp. 2744–2753, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. P. R. Moreno, K. R. Purushothaman, M. Sirol, A. P. Levy, and V. Fuster, “Neovascularization in human atherosclerosis,” Circulation, vol. 113, no. 18, pp. 2245–2252, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. P. Dandona, S. Dhindsa, H. Ghanim, and A. Chaudhuri, “Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade,” Journal of Human Hypertension, vol. 21, no. 1, pp. 20–27, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. J. I. Koga, K. Egashira, T. Matoba et al., “Essential role of angiotensin II type 1a receptors in the host vascular wall, but not the bone marrow, in the pathogenesis of angiotensin II-induced atherosclerosis,” Hypertension Research, vol. 31, no. 9, pp. 1791–1800, 2008. View at Google Scholar · View at Scopus
  45. Z. S. Galis and J. J. Khatri, “Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly,” Circulation Research, vol. 90, no. 3, pp. 251–262, 2002. View at Google Scholar · View at Scopus
  46. J. Chen, D. Li, R. F. Schaefer, and J. L. Mehta, “Inhibitory effect of candesartan and rosuvastatin on CD40 and MMPs expression in Apo-E knockout mice: novel insights into the role of RAS and dyslipidemia in atherogenesis,” Journal of Cardiovascular Pharmacology, vol. 44, no. 4, pp. 446–452, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Luchtefeld, K. Grote, C. Grothusen et al., “Angiotensin II induces MMP-2 in a p47phox-dependent manner,” Biochemical and Biophysical Research Communications, vol. 328, no. 1, pp. 183–188, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. H. Itoh, M. Mukoyama, R. E. Pratt, G. H. Gibbons, and V. J. Dzau, “Multiple autocrine growth factors modulate vascular smooth muscle cell growth response to angiotensin II,” Journal of Clinical Investigation, vol. 91, no. 5, pp. 2268–2274, 1993. View at Google Scholar · View at Scopus
  49. A. J. Naftilan, R. E. Pratt, and V. J. Dzau, “Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells,” Journal of Clinical Investigation, vol. 83, no. 4, pp. 1419–1424, 1989. View at Google Scholar · View at Scopus
  50. M. J. Pollman, T. Yamada, M. Horiuchi, and G. H. Gibbons, “Vasoactive substances regulate vascular smooth muscle cell apoptosis: countervailing influences of nitric oxide and angiotensin II,” Circulation Research, vol. 79, no. 4, pp. 748–756, 1996. View at Google Scholar · View at Scopus
  51. T. Takagishi, N. Murahashi, S. Azagami, M. Morimatsu, and Y. Sasaguri, “Effect of angiotensin II and thromboxane A2 on the production of matrix metalloproteinase by human aortic smooth muscle cells,” Biochemistry and Molecular Biology International, vol. 35, no. 2, pp. 265–273, 1995. View at Google Scholar · View at Scopus
  52. T. Scott-Burden, A. W. A. Hahn, T. J. Resink, and F. R. Buhler, “Modulation of extracellular matrix by angiotensin II: stimulated glycoconjugate synthesis and growth in vascular smooth muscle cells,” Journal of Cardiovascular Pharmacology, vol. 16, supplement 4, pp. S36–S41, 1990. View at Google Scholar · View at Scopus
  53. R. M. Touyz, “Intracellular mechanisms involved in vascular remodelling of resistance arteries in hypertension: role of angiotensin II,” Experimental Physiology, vol. 90, no. 4, pp. 449–455, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. R. M. Touyz and E. L. Schiffrin, “Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells,” Pharmacological Reviews, vol. 52, no. 4, pp. 639–672, 2000. View at Google Scholar · View at Scopus
  55. T. J. Murphy, R. W. Alexander, K. K. Griendling, M. S. Runge, and K. E. Bernstein, “Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor,” Nature, vol. 351, no. 6323, pp. 233–236, 1991. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. I. H. Schulman, M. S. Zhou, and L. Raij, “Nitric oxide, angiotensin II, and reactive oxygen species in hypertension and atherogenesis,” Current Hypertension Reports, vol. 7, no. 1, pp. 61–67, 2005. View at Google Scholar · View at Scopus
  57. J. B. Laursen, S. Rajagopalan, Z. Galis, M. Tarpey, B. A. Freeman, and D. G. Harrison, “Role of superoxide in angiotensin II-induced but not catecholamine- induced hypertension,” Circulation, vol. 95, no. 3, pp. 588–593, 1997. View at Google Scholar · View at Scopus
  58. K. K. Griendling and G. A. FitzGerald, “Oxidative stress and cardiovascular injury: part I: basic mechanisms and in vivo monitoring of ROS,” Circulation, vol. 108, no. 16, pp. 1912–1916, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. B. Lassègue and R. E. Clempus, “Vascular NAD(P)H oxidases: specific features, expression, and regulation,” American Journal of Physiology, vol. 285, no. 2, pp. R277–R297, 2003. View at Google Scholar · View at Scopus
  60. K. K. Griendling, D. Sorescu, and M. Ushio-Fukai, “NAD(P)H oxidase: role in cardiovascular biology and disease,” Circulation Research, vol. 86, no. 5, pp. 494–501, 2000. View at Google Scholar · View at Scopus
  61. P. A. Barry-Lane, C. Patterson, M. Van Der Merwe et al., “p47phox is required for atherosclerotic lesion progression in ApoE mice (-/-),” Journal of Clinical Investigation, vol. 108, no. 10, pp. 1513–1522, 2001. View at Publisher · View at Google Scholar · View at Scopus
  62. C. Viedt, U. Soto, H. I. Krieger-Brauer et al., “Differential activation of mitogen-activated protein kinases in smooth muscle cells by angiotensin II: involvement of p22phox and reactive oxygen species,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 4, pp. 940–948, 2000. View at Google Scholar · View at Scopus
  63. M. Ushio-Fukai, R. W. Alexander, M. Akers et al., “Reactive oxygen species mediate the activation of Akt/protein kinase B by angiotensin II in vascular smooth muscle cells,” Journal of Biological Chemistry, vol. 274, no. 32, pp. 22699–22704, 1999. View at Publisher · View at Google Scholar · View at Scopus
  64. B. Schieffer, M. Luchtefeld, S. Braun, A. Hilfiker, D. Hilfiker-Kleiner, and H. Drexler, “Role of NAD(P)H oxidase in angiotensin II-induced JAK/STAT signaling and cytokine induction,” Circulation Research, vol. 87, no. 12, pp. 1195–1201, 2000. View at Google Scholar · View at Scopus
  65. A. R. Simon, U. Rai, B. L. Fanburg, and B. H. Cochran, “Activation of the JAK-STAT pathway by reactive oxygen species,” American Journal of Physiology, vol. 275, no. 6, part 1, pp. C1640–C1652, 1998. View at Google Scholar · View at Scopus
  66. A. Warnholtz, G. Nickenig, E. Schulz et al., “Increased NADH-oxidase-mediated superoxide production. In the early stages of atherosclerosis evidence for involvement of the renin-angiotensin system,” Circulation, vol. 99, no. 15, pp. 2027–2033, 1999. View at Google Scholar · View at Scopus
  67. G. Desideri, M. C. Bravi, M. Tucci et al., “Angiotensin II inhibits endothelial cell motility through an AT-dependent oxidant-sensitive decrement of nitric oxide availability,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 7, pp. 1218–1223, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. M. K. Cathcart, “Regulation of superoxide anion production by NADPH oxidase in monocytes/macrophages: contributions to atherosclerosis,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 1, pp. 23–28, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. K. K. Griendling, C. A. Minieri, J. D. Ollerenshaw, and R. W. Alexander, “Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells,” Circulation Research, vol. 74, no. 6, pp. 1141–1148, 1994. View at Google Scholar · View at Scopus
  70. A. W. A. Hahn, “Activation of human peripheral monocytes by angiotensin II,” FEBS Letters, vol. 347, no. 2-3, pp. 178–180, 1994. View at Publisher · View at Google Scholar · View at Scopus
  71. A. R. Brasier, M. Jamaluddin, Y. Han, C. Patterson, and M. S. Runge, “Angiotensin II induces gene transcription through cell-type-dependent effects on the nuclear factor-κB (NF-κB) transcription factor,” Molecular and Cellular Biochemistry, vol. 212, no. 1-2, pp. 155–169, 2000. View at Google Scholar · View at Scopus
  72. M. Graninger, R. Reiter, C. Drucker, E. Minar, and B. Jilma, “Angiotensin receptor blockade decreases markers of vascular inflammation,” Journal of Cardiovascular Pharmacology, vol. 44, no. 3, pp. 335–339, 2004. View at Publisher · View at Google Scholar
  73. E. Shagdarsuren, M. Wellner, J. H. Braesen et al., “Complement activation in angiotensin II-induced organ damage,” Circulation Research, vol. 97, no. 7, pp. 716–724, 2005. View at Publisher · View at Google Scholar · View at PubMed
  74. M. Epstein, “Aldosterone and the hypertensive kidney: its emerging role as a mediator of progressive renal dysfunction: a paradigm shift,” Journal of Hypertension, vol. 19, no. 5, pp. 829–842, 2001. View at Publisher · View at Google Scholar
  75. T. Hayek, J. Attias, R. Coleman et al., “The angiotensin-converting enzyme inhibitor, fosinopril, and the angiotensin II receptor antagonist, losartan, inhibit LDL oxidation and attenuate atherosclerosis independent of lowering blood pressure in apolipoprotein E deficient mice,” Cardiovascular Research, vol. 44, no. 3, pp. 579–587, 1999. View at Publisher · View at Google Scholar
  76. S. Keidar, R. Heinrich, M. Kaplan, T. Hayek, and M. Aviram, “Angiotensin II administration to atherosclerotic mice increases macrophage uptake of oxidized LDL: a possible role for interleukin-6,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 21, no. 9, pp. 1464–1469, 2001. View at Google Scholar
  77. O. Soehnlein, S. Eskafi, A. Schmeisser, H. Kloos, W. G. Daniel, and C. D. Garlichs, “Atorvastatin induces tissue transglutaminase in human endothelial cells,” Biochemical and Biophysical Research Communications, vol. 322, no. 1, pp. 105–109, 2004. View at Publisher · View at Google Scholar · View at PubMed
  78. F. Montecucco, A. Pende, and F. MacH, “The renin-angiotensin system modulates inflammatory processes in atherosclerosis: evidence from basic research and clinical studies,” Mediators of Inflammation, vol. 2009, Article ID 752406, 2009. View at Publisher · View at Google Scholar · View at PubMed
  79. U. N. Das, “Is angiotensin-II an endogenous pro-inflammatory molecule?” Medical Science Monitor, vol. 11, no. 5, pp. RA155–RA162, 2005. View at Google Scholar
  80. V. Fuster and J. Sanz, “Vascular inflammation,” Journal of the American Society of Hypertension, vol. 1, no. 1, pp. 68–81, 2007. View at Publisher · View at Google Scholar · View at PubMed
  81. A. E. Vendrov, Z. S. Hakim, N. R. Madamanchi, M. Rojas, C. Madamanchi, and M. S. Runge, “Atherosclerosis is attenuated by limiting superoxide generation in both macrophages and vessel wall cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 12, pp. 2714–2721, 2007. View at Publisher · View at Google Scholar · View at PubMed
  82. P. E. Tummala, XI. L. Chen, C. L. Sundell 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, vol. 100, no. 11, pp. 1223–1229, 1999. View at Google Scholar
  83. I. C. Haznedaroglu and Y. Beyazit, “Pathobiological aspects of the local bone marrow renin—;angiotensin system: a review,” Journal of the Renin-Angiotensin-Aldosterone System, vol. 11, no. 4, pp. 205–213, 2010. View at Publisher · View at Google Scholar · View at PubMed
  84. I. C. Haznedaroglu and M. A. Öztürk, “Towards the understanding of the local hematopoietic bone marrow renin-angiotensin system,” International Journal of Biochemistry and Cell Biology, vol. 35, no. 6, pp. 867–880, 2003. View at Publisher · View at Google Scholar
  85. V. J. Jokubaitis, L. Sinka, R. Driessen et al., “Angiotensin-converting enzyme (CD143) marks hematopoietic stem cells in human embryonic, fetal, and adult hematopoietic tissues,” Blood, vol. 111, no. 8, pp. 4055–4063, 2008. View at Publisher · View at Google Scholar · View at PubMed
  86. E. T. Zambidis, T. S. Park, W. Yu et al., “Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells,” Blood, vol. 112, no. 9, pp. 3601–3614, 2008. View at Publisher · View at Google Scholar · View at PubMed
  87. H. Goker, I. C. Haznedaroglu, Y. Beyazit et al., “Local umbilical cord blood renin-angiotensin system,” Annals of Hematology, vol. 84, no. 5, pp. 277–281, 2005. View at Publisher · View at Google Scholar · View at PubMed
  88. K. Acar, Y. Beyazit, A. Sucak et al., “Alterations in the 'local umbilical cord blood renin-angiotensin system' during pre-eclampsia,” Acta Obstetricia et Gynecologica Scandinavica, vol. 86, no. 10, pp. 1193–1199, 2007. View at Publisher · View at Google Scholar · View at PubMed
  89. M. A. Öztürk, G. S. Güven, and I. C. Haznedaroglu, “How hematopoietic stem cells know and act in cardiac microenvironment for stem cell plasticity? Impact of local renin-angiotensin systems,” Medical Hypotheses, vol. 63, no. 5, pp. 866–874, 2004. View at Publisher · View at Google Scholar · View at PubMed
  90. S. Aksu, Y. Beyazit, I. C. Haznedaroglu et al., “Enhanced expression of the local haematopoietic bone marrow renin-angiotensin system in polycythemia rubra vera,” Journal of International Medical Research, vol. 33, no. 6, pp. 661–667, 2005. View at Google Scholar
  91. S. Aksu, Y. Beyazit, I. C. Haznedaroglu et al., “Over-expression of angiotensin-converting enzyme (CD 143) on leukemic blasts as a clue for the activated local bone marrow RAS in AML,” Leukemia and Lymphoma, vol. 47, no. 5, pp. 891–896, 2006. View at Publisher · View at Google Scholar · View at PubMed
  92. Y. Beyazit, S. Aksu, I. C. Haznedaroglu et al., “Overexpression of the local bone marrow renin-angiotensin system in acute myeloid leukemia,” Journal of the National Medical Association, vol. 99, no. 1, pp. 57–63, 2007. View at Google Scholar
  93. E. Koca, I. C. Haznedaroglu, K. Acar et al., “Renin-angiotensin system expression in the K562 human erythroleukaemic cell line,” Journal of the Renin-Angiotensin-Aldosterone System, vol. 8, no. 3, pp. 145–147, 2007. View at Publisher · View at Google Scholar · View at PubMed
  94. E. Koca, I. C. Haznedaroglu, A. Uner et al., “Angiotensin-converting enzyme expression of the lymphoma-associated macrophages in the lymph nodes of Hodgkin's disease,” Journal of the National Medical Association, vol. 99, no. 11, pp. 1243–1247, 2007. View at Google Scholar
  95. G. G. Wulf, G. Jahns-Streusel, R. Nobiling et al., “Renin in acute myeloid leukaemia blasts,” British Journal of Haematology, vol. 100, no. 2, pp. 335–337, 1998. View at Publisher · View at Google Scholar
  96. G. G. Wulf, G. Jahns-Streubel, F. Strutz et al., “Paraneoplastic hypokalemia in acute myeloid leukemia: a case of renin activity in AML blast cells,” Annals of Hematology, vol. 73, no. 3, pp. 139–141, 1996. View at Publisher · View at Google Scholar
  97. R. P. Pinto, K. K. Wang, H. Khoury, A. D. Schimmer, and M. D. Minden, “Aberrant expression of angiotensin in acute myeloid leukemia,” Blood, vol. 102, p. 2124A, 2004. View at Google Scholar
  98. A. Takeda, C. Goolsby, and N. R. Yaseen, “NUP98-HOXA9 induces long-term proliferation and blocks differentiation of primary human CD34 hematopoietic cells,” Cancer Research, vol. 66, no. 13, pp. 6628–6637, 2006. View at Publisher · View at Google Scholar · View at PubMed
  99. I. C. Haznedaro, M. Arici, and Y. Büyükaşik, “A unifying hypothesis for the renin-angiotensin system and hematopoiesis: sticking the pieces together with the JAK-STAT pathway,” Medical Hypotheses, vol. 54, no. 1, pp. 80–83, 2000. View at Publisher · View at Google Scholar
  100. M. Sayitoglu, I. C. Haznedaroǧlu, O. Hatirnaz et al., “Effects of imatinib mesylate on Renin-Angiotensin System (RAS) activity during the clinical course of chronic myeloid leukaemia,” Journal of International Medical Research, vol. 37, no. 4, pp. 1018–1028, 2009. View at Google Scholar
  101. S. Verstovsek, H. Kantarjian, R. A. Mesa et al., “Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis,” New England Journal of Medicine, vol. 363, no. 12, pp. 1117–1127, 2010. View at Publisher · View at Google Scholar · View at PubMed
  102. M. M. Vrsalovic, V. Pejsa, T. S. Veic et al., “Bone marrow renin-angiotensin system expression in polycythemia vera and essential thrombocythemia depends on JAK2 mutational status,” Cancer Biology and Therapy, vol. 6, no. 9, pp. 1434–1436, 2007. View at Google Scholar
  103. K. Savary, A. Michaud, J. Favier, E. Larger, P. Corvol, and J. M. Gasc, “Role of the renin-angiotensin system in primitive erythropoiesis in the chick embryo,” Blood, vol. 105, no. 1, pp. 103–110, 2005. View at Publisher · View at Google Scholar · View at PubMed
  104. E. T. Zambidis, B. Peault, T. S. Park, F. Bunz, and C. I. Civin, “Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development,” Blood, vol. 106, no. 3, pp. 860–870, 2005. View at Publisher · View at Google Scholar · View at PubMed
  105. A. Peters, P. W. Burridge, M. V. Pryzhkova et al., “Challenges and strategies for generating therapeutic patient-specific hemangioblasts and hematopoietic stem cells from human pluripotent stem cells,” International Journal of Developmental Biology, vol. 54, no. 6-7, pp. 965–990, 2010. View at Publisher · View at Google Scholar · View at PubMed
  106. C. Hubert, K. Savary, J. M. Gasc, and P. Corvol, “The hematopoietic system: a new niche for the renin-angiotensin system,” Nature Clinical Practice Cardiovascular Medicine, vol. 3, no. 2, pp. 80–85, 2006. View at Publisher · View at Google Scholar · View at PubMed
  107. S. C. Heffelfinger, “The renin angiotensin system in the regulation of angiogenesis,” Current Pharmaceutical Design, vol. 13, no. 12, pp. 1215–1229, 2007. View at Publisher · View at Google Scholar
  108. F. P. Limbourg and H. Drexler, “Bone marrow stem cells for myocardial infarction: effector or mediator?” Circulation Research, vol. 96, no. 1, pp. 6–8, 2005. View at Publisher · View at Google Scholar · View at PubMed
  109. R. Ross, “Atherosclerosis-an inflammatory disease,” The New England Journal of Medicine, vol. 340, pp. 115–126, 1999. View at Google Scholar
  110. S. M. Schwartz, “Smooth muscle migration in atherosclerosis and restenosis,” Journal of Clinical Investigation, vol. 100, no. 11, pp. S87–S89, 1997. View at Google Scholar
  111. C. Bauters and J. M. Isner, “The biology of restenosis,” Progress in Cardiovascular Diseases, vol. 40, no. 2, pp. 107–116, 1997. View at Publisher · View at Google Scholar
  112. P. Libby, D. Schwartz, E. Brogi, H. Tanaka, and S. K. Clinton, “A cascade model for restenosis: a special case of atherosclerosis progression,” Circulation, vol. 86, no. 6, supplement, pp. III47–III52, 1992. View at Google Scholar
  113. P. Carmeliet, L. Moons, J. M. Stassen et al., “Vascular wound healing and neointima formation induced by perivascular electric injury in mice,” American Journal of Pathology, vol. 150, no. 2, pp. 761–776, 1997. View at Google Scholar
  114. T. Asahara, H. Masuda, T. Takahashi et al., “Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization,” Circulation Research, vol. 85, no. 3, pp. 221–228, 1999. View at Google Scholar
  115. T. Asahara, T. Murohara, A. Sullivan et al., “Isolation of putative progenitor endothelial cells for angiogenesis,” Science, vol. 275, no. 5302, pp. 964–967, 1997. View at Publisher · View at Google Scholar
  116. K. Ito, A. Hirao, F. Arai et al., “Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells,” Nature Medicine, vol. 12, no. 4, pp. 446–451, 2006. View at Publisher · View at Google Scholar · View at PubMed
  117. W. Strawn, R. Richmond, and C. Ferrario, “A new understanding of atherosclerosis: the bone marrow response-to-lipid hypothesis,” in Heart Disease: Pathogenesis, Diagnosis and Treatment, pp. 183–188, 3rd World Congress on Heart Disease, Washington, DC, USA, 2003. View at Google Scholar
  118. W. B. Strawn and C. M. Ferrario, “Angiotensin II AT receptor blockade normalizes CD11b(+) monocyte production in bone marrow of hypercholesterolemic monkeys,” Atherosclerosis, vol. 196, no. 2, pp. 624–632, 2008. View at Publisher · View at Google Scholar · View at PubMed
  119. D. Fukuda and M. Sata, “The renin-angiotensin system: a potential modulator of endothelial progenitor cells,” Hypertension Research, vol. 30, no. 11, pp. 1017–1018, 2007. View at Publisher · View at Google Scholar · View at PubMed
  120. L. A. Cassis, D. L. Rateri, H. Lu, and A. Daugherty, “Bone marrow transplantation reveals that recipient AT1a receptors are required to initiate angiotensin II-induced atherosclerosis and aneurysms,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 2, pp. 380–386, 2007. View at Publisher · View at Google Scholar · View at PubMed
  121. Y. Tsubakimoto, H. Yamada, H. Yokoi et al., “Bone marrow angiotensin AT1 receptor regulates differentiation of monocyte lineage progenitors from hematopoietic stem cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 29, no. 10, pp. 1529–1536, 2009. View at Publisher · View at Google Scholar · View at PubMed
  122. T. Yamada, T. Kondo, Y. Numaguchi et al., “Angiotensin II receptor blocker inhibits neointimal hyperplasia through regulation of smooth muscle-like progenitor cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 11, pp. 2363–2369, 2007. View at Publisher · View at Google Scholar · View at PubMed
  123. H. Lu, D. L. Rateri, D. L. Feldman et al., “Renin inhibition reduces hypercholesterolemia-induced atherosclerosis in mice,” Journal of Clinical Investigation, vol. 118, no. 3, pp. 984–993, 2008. View at Publisher · View at Google Scholar · View at PubMed
  124. H. Kato, J. Ishida, K. Nagano et al., “Deterioration of atherosclerosis in mice lacking angiotensin II type 1A receptor in bone marrow-derived cells,” Laboratory Investigation, vol. 88, no. 7, pp. 731–739, 2008. View at Publisher · View at Google Scholar · View at PubMed
  125. D. Fukuda, S. Enomoto, R. Nagai, and M. Sata, “Inhibition of renin-angiotensin system attenuates periadventitial inflammation and reduces atherosclerotic lesion formation,” Biomedicine and Pharmacotherapy, vol. 63, no. 10, pp. 754–761, 2009. View at Publisher · View at Google Scholar · View at PubMed