Abstract
Angiotensin II promotes vascular inflammation, which plays important roles in vascular injury. In this study, we found that angiotensin II-stimulated human endothelial cells increased the release of a CXC chemokine, IP-10, according to an antibody array. IP-10 expression was higher in the endothelium of coronary blood vessels in mice infused with angiotensin II than in control. Quantitative real-time PCR analysis revealed that angiotensin II significantly increased IP-10 mRNA expression compared to control. Pretreatment with valsartan, but not with PD123319, blocked angiotensin II-induced IP-10 mRNA expression. IP-10 levels in conditioned media detected by ELISA increased in response to angiotensin II compared to control, which was blocked by the pretreatment with valsartan. These data indicate that angiotensin II stimulates IP-10 production from endothelial cells via angiotensin II type 1 receptors. In endothelial cells, IP-10 significantly increased mRNA expression of renin, angiotensin-converting enzyme, and angiotensinogen. IP-10 also increased angiotensin II levels in conditioned media compared to control. Angiotensin II significantly increased mRNA expression of renin, angiotensin converting enzyme and angiotensinogen, which was blocked by neutralization of IP-10 with antibody in endothelial cells. IP-10 neutralization with antibody blocked angiotensin II-induced apoptosis and cell senescence in endothelial cells. These data indicate that IP-10 is involved not only in leukocyte-endothelial interaction but also in the circuit of endothelial renin-angiotensin system activation that potentially promotes atherosclerosis.
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Ruiz-Ortega M, Lorenzo O, Rupérez M, et al: Role of the renin-angiotensin system in vascular diseases: expanding the field. Hypertension 2001; 38: 1382–1387.
Suzuki Y, Ruiz-Ortega M, Lorenzo O, Ruperez M, Esteban V, Egido J : Inflammation and angiotensin II. Int J Biochem Cell Biol 2003; 35: 881–900.
Lavoie JL, Sigmund CD : Minireview: overview of the renin-angiotensin system—an endocrine and paracrine system. Endocrinology 2003; 144: 2179–2183.
Paul M, Poyan Mehr A, Kreutz R : Physiology of local renin-angiotensin systems. Physiol Rev 2006; 86: 747–803.
Schmidt-Ott KM, Kagiyama S, Phillips MI : The multiple actions of angiotensin II in atherosclerosis. Regul Pept 2000; 93: 65–77.
Charo IF, Ransohoff RM : The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 2006; 354: 610–621.
Weber C, Schober A, Zernecke A : Chemokines: key regulators of mononuclear cell recruitment in atherosclerotic vascular disease. Arterioscler Thromb Vasc Biol 2004; 24: 1997–2008.
Braunersreuther V, Mach F, Steffens S : The specific role of chemokines in atherosclerosis. Thromb Haemost 2007; 97: 714–721.
Reape TJ, Groot PH : Chemokines and atherosclerosis. Atherosclerosis 1999; 147: 213–225.
Shin WS, Szuba A, Rockson SG : The role of chemokines in human cardiovascular pathology: enhanced biological insights. Atherosclerosis 2002; 160: 91–102.
Ruiz-Ortega M, Bustos C, Hernandez-Presa MA, Lorenzo O, Plaza JJ, Egido J : Angiotensin II participates in mononuclear cell recruitment in experimental immune complex nephritis through nuclear factor-kappa B activation and monocyte chemoattractant protein-1 synthesis. J Immunol 1998; 161: 430–439.
Hernández-Presa M, Bustos C, Ortego M, Tuñon J, Ruiz-Ortega M, Egido J : 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 1997; 95: 1532–1541.
Chen XL, Tummala PE, Olbrych MT, Alexander RW, Medford RM : Angiotensin II induces monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells. Circ Res 1998; 83: 952–959.
Han Y, Runge MS, Brasier AR : Angiotensin II induces interleukin-6 transcriptation in vascular smooth muscle cells through pleiotropic activation of nuclear factor-kappa B transcriptation factors. Circ Res 1999; 84: 695–703.
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. Criculation 2000; 101: 1372–1378.
Ito T, Ikeda U, Yamamoto K, Shimada K : Regulation of interleukin-8 expression by HMG-CoA reductase inhibitors in human vascular smooth muscle cells. Atherosclerosis 2002; 165: 51–55.
Schmeisser A, Soehnlein O, Illmer T, et al: ACE inhibition lowers angiotensin II-induced chemokine expression by reduction of NF-κB activity and AT1 receptor expression. Biochem Biophys Res Commun 2004; 325: 532–540.
Edgell CJ, McDonald CC, Graham JB : Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proc Natl Acad Sci U S A 1983; 80: 3734–3737.
Mach F, Sauty A, Iarossi AS, et al: Differential expression of three T lymphcyte-activating CXC chemokines by human atheroma-associated cell. J Clin Invest 1999; 104: 1041–1050.
Luster AD, Ravetch JV : Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med 1987; 166: 1084–1097.
GarcÃa-López MA, Sánchez-Madrid F, RodrÃguez-Frade JM, et al: CXCR3 chemokine receptor distribution in normal and inflamed tissues: expression on activated lymphocytes, endothelial cells, and dendritic cells. Lab Invest 2001; 81: 409–418.
Bonecchi R, Bianchi G, Bordignon PP, et al: Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 1998; 187: 129–134.
Hillyer P, Mordelet E, Flynn G, Male D : Chemokines, chemokine receptors and adhesion molecules on different human endothelia: discriminating the tissue-specific functions that affect leucocyte migration. Clin Exp Immunol 2003; 134: 431–441.
Romagnani P, Annunziato F, Lasagni L, et al: Cell cycle-dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity. J Clin Invest 2001; 107: 53–63.
Hirase T, Kawashima S, Wong E, et al: Regulation of tight junction permeability and occuludin phosphorylation by RhoA-p160ROCK-dependent and -independent mechanisms. J Biol Chem 2001; 276: 10423–10431.
Fenton M, Barker S, Kurz DJ, Erusalimsky JD : Cellular senescence after single and repeated balloon catheter denudations of rabbit carotid arteries. Arterioscler Thromb Vasc Biol 2001; 21: 220–226.
Bonacchi A, Romagnani P, Romanelli RG, et al: Signal transduction by the chemokine receptor CXCR3: activation of Ras/ERK, Src, and phosphatidylinositol 3-kinase/Akt controls cell migration and proliferation in human vascular pericytes. J Biol Chem 2001; 276: 9945–9954.
Shahabuddin S, Ji R, Wang P, et al: CXCR3 chemokine receptor-induced chemotaxis in human airway epithelial cells: role of p38 MAPK and PI3K signaling pathways. Am J Physiol Cell Physiol 2006; 291: C34–C39.
Taub DD, Lloyd AR, Conlon K, et al: Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med 1993; 177: 1809–1814.
Touyz RM, Schiffrin EL : Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev 2000; 52: 639–672.
Kudoh S, Komuro I, Mizuno T, et al: Angiotensin II stimulates c-Jun NH2-terminal kinase in cultured cardiac myocytes of neonatal rats. Circ Res 1997; 80: 139–146.
Akishita M, Nagai K, Xi H, et al: Renin-angiotensin system modulates oxidative stress-induced endothelial cell apoptosis in rats. Hypertension 2005; 45: 1188–1193.
Wassmann S, Czech T, Eickels M, Fleming I, Böhm M, Nickenig G : Inhibition of diet-induced atherosclerosis and endothelial dysfunction in apolipoprotein E/angiotensin II type 1A receptor double-knockout mice. Circulation 2004; 110: 3062–3067.
Candido R, Allen TJ, Lassila M, et al: Irbesartan but not amlodipine suppresses diabetes-associated atherosclerosis. Circulation 2004; 109: 1536–1542.
Mateo T, Abu Nabah YN, Abu Taha M, et al: Angiotensin II-induced mononuclear leukocyte interactions with arteriolar and venular endothelium are mediated by the release of different CC chemokines. J Immunol 2006; 176: 5577–5586.
Tamassia N, Calzetti F, Ear T, et al: Molecular mechanisms underlying the synergistic induction of CXCL10 by LPS and IFN-γ in human neutrophils. Eur J Immunol 2007; 37: 2627–2634.
Suzuki Y, Gómez-Guerrero C, Shirato I, et al: Susceptibility to T cell-mediated injury in immune complex disease is linked to local activation of renin-angiotensin system: the role of NF-AT pathway. J Immunol 2002; 169: 4136–4146.
Veillard NR, Steffens S, Pelli G, et al: Differential influence of chemokine receptors CCR2 and CXCR3 in development of atherosclerosis in vivo. Circulation 2005: 112: 870–878.
Malhotra R, Sadoshima J, Brosius FC III, Izumo S : Mechanical stretch and angiotensin II differentially upregulate the renin-angiotensin system in cardiac myocytes in vitro. Circ Res 1999; 85: 137–146.
Bader M, Peters J, Baltatu O, Muller DN, Luft FC, Ganten D : Tissue renin-angiotensin systems: new insights from experimental animal models in hypertension research. J Mol Med 2001; 79: 76–102.
Kei K, Hiromi R, Michiko N, et al: Insulin-mediated regulation of the endothelial renin-angiotensin system and vascular cell growth. J Hypertens 2004; 22: 121–127.
Xiao F, Puddefoot JR, Vinson GP : The expression of renin and the formation of angiotensinII in bovine aortic endothelial cells. J Endocrinol 2000; 164: 207–214.
Kukhtina NB, Arefieva TI, Krasnikova TL : Intracellular signal cascade in CD4+ T-lymphocyte migration stimulated by interferon-γ-inducible protein-10. Biochemistry 2005; 70: 652–656.
Kouroumalis A, Nibbs RJ, Aptel H, Wright KL, Kolios G, Ward SG : The chemokines CXCL9, CXCL10, and CXCL11 differentially stimulate Gαi-independent signaling and actin responses in human intestinal myofibroblasts. J Immunol 2005; 175: 5403–5411.
Shen Q, Zhang R, Bhat NR : MAP kinase regulation of IP10/CXCL10 chemokine gene expression in microglial cells. Brain Res 2006; 1086: 9–16.
Indraccolo S, Pfeffer U, Minuzzo S, et al: Identification of genes selectively regulated by IFNs in endothelial cells. J Immunol 2007; 178: 1122–1135.
Bodnar RJ, Yates CC, Wells A : IP-10 blocks vascular endothelial growth factor-induced endothelial cell motility and tube formation via inhibition of calpain. Circ Res 2006; 98: 617–625.
Liu X, Shi Q, Sigmund CD : Interleukin-1beta attenuates renin gene expression via a mitogen-activated protein kinase kinase-extracellular signal-regulated kinase and signal transducer and activator of transcription 3-dependent mechanism in As4.1 cells. Endocrinology 2006; 147: 6011–6018.
Baumann H, Wang Y, Richards CD, Jones CA, Block TA, Gross KW : Endotoxin-induced renal inflammatory response. J Biol Chem 2000; 275: 22014–22019.
Brasier AR, Recinos A III, Eledrisi MS : Vascular inflammation and the renin-angiotensin system. Arterioscler Thromb Vasc Biol 2002; 22: 1257–1266.
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Ide, N., Hirase, T., Nishimoto-Hazuku, A. et al. Angiotensin II Increases Expression of IP-10 and the Renin-Angiotensin System in Endothelial Cells. Hypertens Res 31, 1257–1267 (2008). https://doi.org/10.1291/hypres.31.1257
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DOI: https://doi.org/10.1291/hypres.31.1257
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