Aldosterone as a modulator of immunity: Implications in the organ damage

Journal of Hypertension

Volumn 29, Issue 9, 2011, Pages 1684-1692

  Herrada, Andrés A ^a   Campino, Carmen ^b   Amador, Cristián A ^a   Michea, Luis F ^a   Fardella, Carlos E ^a,b   Kalergis, Alexis M ^a,c  

^a Pontificia Universidad Católica de Chile   (Chile)

^b Departamento de Endocrinologý a   (Chile)

^c PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE   (Chile)

Author keywords

aldosterone; dendritic cells; immune response; T cells; vascular damage

Indexed keywords

3 NITROTYROSINE; ALDOSTERONE; CALCIUM ION; CELL MARKER; CYCLIC AMP; CYCLOOXYGENASE 2; ED1 PROTEIN; EPLERENONE; GUANINE NUCLEOTIDE BINDING PROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 1BETA; LYMPHOCYTE FUNCTION ASSOCIATED ANTIGEN 1; MINERALOCORTICOID RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE; MONOCYTE CHEMOTACTIC PROTEIN 1; OSTEOPONTIN; PHOSPHATIDYLINOSITOL 3 KINASE; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROSTAGLANDIN E2; PROTEIN KINASE B; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SPIRONOLACTONE; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADAPTIVE IMMUNITY; ADRENERGIC SYSTEM; ALDOSTERONE BLOOD LEVEL; ARTERIAL STIFFNESS; B LYMPHOCYTE; BREAST TENDERNESS; CALCIUM CELL LEVEL; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DEATH; CELLULAR IMMUNITY; COLLAGEN SYNTHESIS; DENDRITIC CELL; DIABETIC PATIENT; DRUG COST; EXTRACELLULAR MATRIX; GENE EXPRESSION; GYNECOMASTIA; HEART MUSCLE CELL; HEART MUSCLE FIBROSIS; HEART VENTRICLE; HUMAN; HYPERTENSION; IMPOTENCE; INFLAMMATION; INFLAMMATORY CELL; INNATE IMMUNITY; KIDNEY INJURY; LEUKOCYTE ADHERENCE; LIBIDO DISORDER; LOW DRUG DOSE; MACROPHAGE; MENSTRUATION DISORDER; MONOCYTE; NONHUMAN; ORGAN INJURY; OXIDATIVE STRESS; PATHOGENESIS; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIMARY HYPERALDOSTERONISM; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEINURIA; REVIEW; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; T LYMPHOCYTE ACTIVATION; TH1 CELL; TH17 CELL; TH2 CELL; UPREGULATION; VASCULAR SMOOTH MUSCLE; WILD TYPE;

EID: 80051953603     PISSN: 02636352     EISSN: 14735598     Source Type: Journal    
DOI: 10.1097/HJH.0b013e32834a4c75     Document Type: Review

References (99)

1. Foster RH, MacFarlane CH, Bustamante MO. Recent progress in understanding aldosterone secretion. Gen Pharmacol 1997; 28:647-651. (Pubitemid 27244412)
2. Tait SA, Tait JF. The correspondence of S.A.S. Simpson and J.F. Tait with T. Reichstein during their collaborative work on the isolation and elucidation of the structure of electrocortin (later aldosterone). Steroids 1998; 63: 440-453.
3. Spat A, Hunyady L. Control of aldosterone secretion: a model for convergence in cellular signaling pathways. Physiol Rev 2004; 84:489-539. (Pubitemid 38365491)
4. Davis JO. Mechanisms of salt and water retention in congestive heart failure. The importance of aldosterone. Am J Med 1960; 29:486-507.
5. Farman N, Rafestin-Oblin ME. Multiple aspects of mineralocorticoid selectivity. Am J Physiol Renal Physiol 2001; 280:F181-F192.
6. Mader IJ, Iseri LT. Spontaneous hypopotassemia, hypomagnesemia, alkalosis and tetany due to hypersecretion of corticosterone-like mineralocorticoid. Am J Med 1955; 19:976-988.
7. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360:1903-1913. (Pubitemid 35472129)
8. Stier CT Jr, Chander PN, Rocha R. Aldosterone as a mediator in cardiovascular injury. Cardiol Rev 2002; 10:97-107. (Pubitemid 34246658)
9. Lombes M, Alfaidy N, Eugene E, Lessana A, Farman N, Bonvalet JP. Prerequisite for cardiac aldosterone action. Mineralocorticoid receptor and beta-hydroxysteroid dehydrogenase in the human heart. Circulation 1995; 92: 175-182
10. Takeda Y, Miyamori I, Inaba S, Furukawa K, Hatakeyama H, Yoneda T, et al. Vascular aldosterone in genetically hypertensive rats. Hypertension 1997; 29:45-48. (Pubitemid 27078339)
11. Zhou MY, Gomez-Sanchez CE, Gomez-Sanchez EP. An alternatively spliced rat mineralocorticoid receptor mRNA causing truncation of the steroid binding domain. Mol Cell Endocrinol 2000; 159: 125-131. (Pubitemid 30067646)
12. Rickard AJ, Morgan J, Tesch G, Funder JW, Fuller PJ, YoungMJ. Deletion of mineralocorticoid receptors from macrophages protects against deoxycorticosterone/salt-induced cardiac fibrosis and increased blood pressure. Hypertension 2009; 54:537-543.
13. Rickard AJ, Young MJ. Corticosteroid receptors, macrophages and cardiovascular disease. J Mol Endocrinol 2009; 42:449-459.
14. Rocha R, Chander PN, Khanna K, Zuckerman A, Stier CT Jr. Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats. Hypertension 1998; 31:451-458.
15. Swedberg K, Eneroth P, Kjekshus J, Wilhelmsen L. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. Circulation 1990; 82:1730-1736. (Pubitemid 20367976)
16. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348:1309-1321. (Pubitemid 36384098)
17. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341:709-717. (Pubitemid 29407370)
18. Pitt B, Reichek N, Willenbrock R, Zannad F, Phillips RA, Roniker B, et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study. Circulation 2003; 108:1831-1838. (Pubitemid 37296092)
19. Rudolph AE, Rocha R, McMahon EG. Aldosterone target organ protection by eplerenone. Mol Cell Endocrinol 2004; 217:229-238. (Pubitemid 38596647)
20. Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system. Circulation 1991; 83:1849-1865.
21. Brown NJ. Aldosterone and vascular inflammation. Hypertension 2008; 51:161-167. (Pubitemid 351159920)
22. Weber KT, Brilla CG, Campbell SE, Guarda E, Zhou G, Sriram K. Myocardial fibrosis: role of angiotensin II and aldosterone. Basic Res Cardiol 1993; 88 (Suppl 1):107-124. (Pubitemid 23226442)
23. Sun Y, Ratajska A, Zhou G, Weber KT. Angiotensin-converting enzyme and myocardial fibrosis in the rat receiving angiotensin II or aldosterone. J Lab Clin Med 1993; 122:395-403. (Pubitemid 23346774)
24. Sun Y, Ramires FJ, Weber KT. Fibrosis of atria and great vessels in response to angiotensin II or aldosterone infusion. Cardiovasc Res 1997; 35:138-147. (Pubitemid 27374751)
25. Neumann S, Huse K, Semrau R, Diegeler A, Gebhardt R, Buniatian GH, Scholz GH. Aldosterone and D-glucose stimulate the proliferation of human cardiac myofibroblasts in vitro. Hypertension 2002; 39:756-760. (Pubitemid 34252870)
26. Bunda S, Liu P, Wang Y, Liu K, Hinek A. Aldosterone induces elastin production in cardiac fibroblasts through activation of insulin-like growth factor-I receptors in a mineralocorticoid receptor-independent manner. Am J Pathol 2007; 171:809-819. (Pubitemid 47440980)
27. Brilla CG, Matsubara LS, Weber KT. Antialdosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. J Mol Cell Cardiol 1993; 25:563-575. (Pubitemid 23208145)
28. Farquharson CA, Struthers AD. Aldosterone induces acute endothelial dysfunction in vivo in humans: evidence for an aldosterone-induced vasculopathy. Clin Sci (Lond) 2002; 103:425-431. (Pubitemid 35193248)
29. Leibovitz E, Ebrahimian T, Paradis P, Schiffrin EL. Aldosterone induces arterial stiffness in absence of oxidative stress and endothelial dysfunction. J Hypertens 2009; 27:2192-2200.
30. Lacolley P, Labat C, Pujol A, Delcayre C, Benetos A, Safar M. Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats: effects of eplerenone. Circulation 2002; 106:2848-2853. (Pubitemid 35396986)
31. Lombes M, Farman N, Bonvalet JP, Zennaro MC. Identification and role of aldosterone receptors in the cardiovascular system. Ann Endocrinol (Paris) 2000; 61:41-46. (Pubitemid 30246167)
32. Golestaneh N, Klein C, Valamanesh F, Suarez G, Agarwal MK, Mirshahi M. Mineralocorticoid receptor-mediated signaling regulates the ion gated sodium channel in vascular endothelial cells and requires an intact cytoskeleton. Biochem Biophys Res Commun 2001; 280:1300-1306. (Pubitemid 32917785)
33. Oberleithner H, Ludwig T, Riethmuller C, Hillebrand U, Albermann L, Schafer C, et al. Human endothelium: target for aldosterone. Hypertension 2004; 43:952-956. (Pubitemid 38579897)
34. Jaffe IZ, Mendelsohn ME. Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ Res 2005; 96:643-650. (Pubitemid 40478331)
35. Caprio M, Newfell BG, la Sala A, Baur W, Fabbri A, Rosano G, et al. Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion. Circ Res 2008; 102:1359-1367.
36. Takeda Y, Yoneda T, Demura M, Miyamori I, Mabuchi H. Cardiac aldosterone production in genetically hypertensive rats. Hypertension 2000; 36:495-500.
37. Yamamoto N, Yasue H, Mizuno Y, Yoshimura M, Fujii H, Nakayama M, et al. Aldosterone is produced from ventricles in patients with essential hypertension. Hypertension 2002; 39:958-962. (Pubitemid 34547793)
38. Ye P, Kenyon CJ, MacKenzie SM, Jong AS, Miller C, Gray GA, et al. The aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes are not expressed in the rat heart. Endocrinology 2005; 146:5287-5293. (Pubitemid 41653041)
39. Gomez-Sanchez EP, Ahmad N, Romero DG, Gomez-Sanchez CE. Origin of aldosterone in the rat heart. Endocrinology 2004; 145:4796-4802. (Pubitemid 39551092)
40. Dworkin LD, Hostetter TH, Rennke HG, Brenner BM. Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. J Clin Invest 1984; 73:1448-1461.
41. Rocha R, Chander PN, Zuckerman A, Stier CT Jr. Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension 1999; 33:232-237. (Pubitemid 29065665)
42. Nishiyama A, Yao L, Nagai Y, Miyata K, Yoshizumi M, Kagami S, et al. Possible contributions of reactive oxygen species and mitogen-activated protein kinase to renal injury in aldosterone/salt-induced hypertensive rats. Hypertension 2004; 43:841-848. (Pubitemid 38405598)
43. Chrysostomou A, Becker G. Spironolactone in addition to ACE inhibition to reduce proteinuria in patients with chronic renal disease. N Engl J Med 2001; 345:925-926.
44. Sun Y, Ahokas RA, Bhattacharya SK, Gerling IC, Carbone LD, Weber KT. Oxidative stress in aldosteronism. Cardiovasc Res 2006; 71:300-309.
45. Ahokas RA, Warrington KJ, Gerling IC, Sun Y, Wodi LA, Herring PA, et al. Aldosteronism and peripheral blood mononuclear cell activation: a neuroendocrine-immune interface. Circ Res 2003; 93:e124-e135.
46. Sun Y, Zhang J, Lu L, Chen SS, Quinn MT, Weber KT. Aldosterone-induced inflammation in the rat heart: role of oxidative stress. Am J Pathol 2002; 161:1773-1781. (Pubitemid 35265535)
47. Hisaki R, Fujita H, Saito F, Kushiro T. Tempol attenuates the development of hypertensive renal injury in Dahl salt-sensitive rats. Am J Hypertens 2005; 18:707-713. (Pubitemid 40692440)
48. Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML, McMahon EG. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int 2003; 63:1791-1800. (Pubitemid 36513325)
49. Lam EY, Funder JW, Nikolic-Paterson DJ, Fuller PJ, Young MJ. Mineralocorticoid receptor blockade but not steroid withdrawal reverses renal fibrosis in deoxycorticosterone/salt rats. Endocrinology 2006; 147:3623-3629. (Pubitemid 43901155)
50. Usher MG, Duan SZ, Ivaschenko CY, Frieler RA, Berger S, Schutz G, et al. Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice. J Clin Invest 2010; 120:3350-3364.
51. Lother A, Berger S, Gilsbach R, Rosner S, Ecke A, Barreto F, et al. Ablation of mineralocorticoid receptors in myocytes but not in fibroblasts preserves cardiac function. Hypertension 2011; 57:746-754.
52. Jaisser F, Swynghedauw B, Delcayre C. The mineralocorticoid receptor in heart: different effects in different cells. Hypertension 2011; 57:679-680.
53. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7:145-173. (Pubitemid 19138011)
54. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 2006; 24:179-189. (Pubitemid 43214587)
55. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006; 441:235-238.
56. Chung DR, Kasper DL, Panzo RJ, Chitnis T, Grusby MJ, Sayegh MH, Tzianabos AO. CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism. J Immunol 2003; 170:1958-1963. (Pubitemid 36197415)
57. Infante-Duarte C, Horton HF, Byrne MC, Kamradt T. Microbial lipopeptides induce the production of IL-17 in Th cells. J Immunol 2000; 165:6107-6115.
58. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 2006; 441:231-234.
59. Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol 2006; 177:566-573. (Pubitemid 43939170)
60. Bush KA, Farmer KM, Walker JS, Kirkham BW. Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum 2002; 46:802-805. (Pubitemid 34214263)
61. Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol 2008; 127:385-393.
62. Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 2007; 204:2449-2460. (Pubitemid 47529329)
63. Schiffrin EL. T lymphocytes: a role in hypertension? Curr Opin Nephrol Hypertens 2010; 19:181-186.
64. Bu DX, Lichtman AH. T cells and blood vessels: costimulation turns up the pressure. Circulation 2010; 122:2495-2498.
65. Madhur MS, Lob HE, McCann LA, Iwakura Y, Blinder Y, Guzik TJ, Harrison DG. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension 2010; 55:500-507.
66. Marvar PJ, Thabet SR, Guzik TJ, Lob HE, McCann LA, Weyand C, et al. Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension. Circ Res 2010; 107:263-270.
67. Huang BS, Ahmadi S, Ahmad M, White RA, Leenen FH. Central neuronal activation and pressor responses induced by circulating ANG II: role of the brain aldosterone-'ouabain' pathway. Am J Physiol Heart Circ Physiol 2010; 299:H422-H430.
68. Lemarie CA, Simeone SM, Nikonova A, Ebrahimian T, Deschenes ME, Coffman TM, et al. Aldosterone-induced activation of signaling pathways requires activity of angiotensin type 1a receptors. Circ Res 2009; 105:852-859.
69. Lal A, Veinot JP, Leenen FH. Critical role of CNS effects of aldosterone in cardiac remodeling postmyocardial infarction in rats. Cardiovasc Res 2004; 64:437-447. (Pubitemid 39505423)
70. Francis J, Weiss RM, Wei SG, Johnson AK, Beltz TG, Zimmerman K, Felder RB. Central mineralocorticoid receptor blockade improves volume regulation and reduces sympathetic drive in heart failure. Am J Physiol Heart Circ Physiol 2001; 281:H2241-H2251.
71. Felder RB. Mineralocorticoid receptors, inflammation and sympathetic drive in a rat model of systolic heart failure. Exp Physiol 2010; 95:19-25.
72. Senokuchi T, Matsumura T, Sakai M, Yano M, Taguchi T, Matsuo T, et al. Statins suppress oxidized low density lipoprotein-induced macrophage proliferation by inactivation of the small G protein-p38 MAPK pathway. J Biol Chem 2005; 280:6627-6633. (Pubitemid 40341214)
73. Herrada AA, Contreras FJ, Marini NP, Amador CA, Gonzalez PA, Cortes CM, et al. Aldosterone promotes autoimmune damage by enhancing Th17-mediated immunity. J Immunol 2010; 184:191-202.
74. Choi JH, Do Y, Cheong C, Koh H, Boscardin SB, Oh YS, et al. Identification of antigen-presenting dendritic cells in mouse aorta and cardiac valves. J Exp Med 2009; 206:497-505.
75. Hoppmann J, Perwitz N, Meier B, Fasshauer M, Hadaschik D, Lehnert H, Klein J. The balance between gluco-and mineralo-corticoid action critically determines inflammatory adipocyte responses. J Endocrinol 2010; 204:153-164.
76. Han JS, Choi BS, Yang CW, Kim YS. Aldosterone-induced TGF-beta1 expression is regulated by mitogen-activated protein kinases and activator protein-1 in mesangial cells. J Korean Med Sci 2009; 24 (Suppl): S195-S203.
77. Xiao J, Shimada M, Liu W, Hu D, Matsumori A. Anti-inflammatory effects of eplerenone on viral myocarditis. Eur J Heart Fail 2009; 11:349-353.
78. Yuan J, Cao AL, Yu M, Lin QW, Yu X, Zhang JH, et al. Th17 cells facilitate the humoral immune response in patients with acute viral myocarditis. J Clin Immunol 2010; 30:226-234.
79. Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab 2004; 89:1045-1050. (Pubitemid 38368386)
80. Fardella CE, Mosso L, Gomez-Sanchez C, Cortes P, Soto J, Gomez L, et al. Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology. J Clin Endocrinol Metab 2000; 85:1863-1867. (Pubitemid 32269290)
81. Mosso L, Carvajal C, Gonzalez A, Barraza A, Avila F, Montero J, et al. Primary aldosteronism and hypertensive disease. Hypertension 2003; 42:161-165. (Pubitemid 36944590)
82. Rossi GP, Di Bello V, Ganzaroli C, Sacchetto A, Cesari M, Bertini A, et al. Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension 2002; 40:23-27. (Pubitemid 34755974)
83. Irita J, Okura T, Manabe S, Kurata M, Miyoshi K, Watanabe S, et al. Plasma osteopontin levels are higher in patients with primary aldosteronism than in patients with essential hypertension. Am J Hypertens 2006; 19:293-297. (Pubitemid 43261511)
84. Carvajal CA, Herrada AA, Castillo CR, Contreras FJ, Stehr CB, Mosso LM, et al. Primary aldosteronism can alter peripheral levels of TGF-beta and TNF-alpha. J Endocrinol Invest 2009; 32:759-765.
85. Grossmann C, Benesic A, Krug AW, Freudinger R, Mildenberger S, Gassner B, Gekle M. Human mineralocorticoid receptor expression renders cells responsive for nongenotropic aldosterone actions. Mol Endocrinol 2005; 19:1697-1710. (Pubitemid 41007884)
86. Christ M, Douwes K, Eisen C, Bechtner G, Theisen K, Wehling M. Rapid effects of aldosterone on sodium transport in vascular smooth muscle cells. Hypertension 1995; 25:117-123.
87. Haseroth K, Gerdes D, Berger S, Feuring M, Gunther A, Herbst C, et al. Rapid nongenomic effects of aldosterone in mineralocorticoid-receptorknockout mice. Biochem Biophys Res Commun 1999; 266:257-261. (Pubitemid 30028801)
88. Gekle M, Silbernagl S, Wunsch S. Nongenomic action of the mineralocorticoid aldosterone on cytosolic sodium in cultured kidney cells. J Physiol 1998; 511 (Pt 1):255-263. (Pubitemid 28421328)
89. Bunda S, Wang Y, Mitts TF, Liu P, Arab S, Arabkhari M, Hinek A. Aldosterone stimulates elastogenesis in cardiac fibroblasts via mineralocorticoid receptor-independent action involving the consecutive activation of Galpha13, c-Src, the insulin-like growth factor-I receptor, and phosphatidylinositol 3-kinase/Akt. J Biol Chem 2009; 284:16633-16647.
90. Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EA, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol 2002; 283:H1802-H1810. (Pubitemid 35217013)
91. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345:1667-1675. (Pubitemid 33126822)
92. Dandona P, Kumar V, Aljada A, Ghanim H, Syed T, Hofmayer D, et al. Angiotensin II receptor blocker valsartan suppresses reactive oxygen species generation in leukocytes, nuclear factor-kappa B, in mononuclear cells of normal subjects: evidence of an antiinflammatory action. J Clin Endocrinol Metab 2003; 88:4496-4501. (Pubitemid 37153762)
93. Maron DJ, Fazio S, Linton MF. Current perspectives on statins. Circulation 2000; 101:207-213. (Pubitemid 30044262)
94. Mira E, Leon B, Barber DF, Jimenez-Baranda S, Goya I, Almonacid L, et al. Statins induce regulatory T cell recruitment via a CCL1 dependent pathway. J Immunol 2008; 181:3524-3534.
95. Ghittoni R, Patrussi L, Pirozzi K, Pellegrini M, Lazzerini PE, Capecchi PL, et al. Simvastatin inhibits T-cell activation by selectively impairing the function of Ras superfamily GTPases. FASEB J 2005; 19:605-607. (Pubitemid 40471259)
96. Fehr T, Kahlert C, Fierz W, Joller-Jemelka HI, Riesen WF, Rickli H, et al. Statin-induced immunomodulatory effects on human T cells in vivo. Atherosclerosis 2004; 175:83-90. (Pubitemid 38746913)
97. Fujita E, Shimizu A, Masuda Y, Kuwahara N, Arai T, Nagasaka S, et al. Statin attenuates experimental antiglomerular basement membrane glomerulonephritis together with the augmentation of alternatively activated macrophages. Am J Pathol 2010; 177:1143-1154.
98. Iruretagoyena MI, Tobar JA, Gonzalez PA, Sepulveda SE, Figueroa CA, Burgos RA, et al. Andrographolide interferes with T cell activation and reduces experimental autoimmune encephalomyelitis in the mouse. J Pharmacol Exp Ther 2005; 312:366-372. (Pubitemid 40096490)
99. Iruretagoyena MI, Sepulveda SE, Lezana JP, Hermoso M, Bronfman M, Gutierrez MA, et al. Inhibition of nuclear factor-kappa B enhances the capacity of immature dendritic cells to induce antigen-specific tolerance in experimental autoimmune encephalomyelitis. J Pharmacol Exp Ther 2006; 318:59-67.