Arterial Hypertension and Interleukins: Potential Therapeutic Target or Future Diagnostic Marker?

Daniela Maria Tanase, Evelina Maria Gosav, Smaranda Radu, Anca Ouatu, Ciprian Rezus, Manuela Ciocoiu, Claudia Florida Costea, Mariana Floria, Daniela Maria Tanase, Evelina Maria Gosav, Smaranda Radu, Anca Ouatu, Ciprian Rezus, Manuela Ciocoiu, Claudia Florida Costea, Mariana Floria

Abstract

Hypertension as a multifactorial pathology is one of the most important cardiovascular risk factors, affecting up to 30-40% of the general population. Complex immune responses are involved in the inflammatory mechanism of hypertension, with evidence pointing to increased inflammatory mediators even in prehypertensive patients. Increased vascular permeability, thrombogenesis, and fibrosis, effects that are associated with sustained hypertension, could be attributed to chronic inflammation. Chronic inflammation triggers endothelial dysfunction via increased production of ROS through proinflammatory cytokines. Increased serum level of proinflammatory cytokines such as IL-1β, IL-6, IL-8, IL-17, IL-23, TGFβ, and TNFα in hypertensive patients has been associated with either increased blood pressure values and/or end-organ damage. Moreover, some cytokines (i.e., IL-6) seem to determine a hypertensive response to angiotensin II, regardless of blood pressure values. Understanding hypertension as an inflammatory-based pathology gives way to new therapeutic targets. As such, conventional cardiovascular drugs (statins, calcium channels blockers, and ACEIs/ARBs) have shown additional anti-inflammatory effects that could be linked to their blood pressure lowering properties. Moreover, anti-inflammatory drugs (mycophenolate mofetil) have been shown to decrease blood pressure in hypertensive patients or prevent its development in normotensive individuals. Further research is needed to evaluate whether drugs targeting hypertensive-linked proinflammatory cytokines, such as monoclonal antibodies, could become a new therapeutic option in treating arterial hypertension.

Figures

Figure 1
Figure 1
Etiology of the inflammatory process. Low level chronic inflammation increases the concentrations of markers and of inflammatory cells, leading to increased production of C-reactive protein (CRP) by the liver, in response to interleukin-6 (IL-6), which provokes a reduction in vasodilation and an increase in vascular damage. TNF-a: tumor necrosis factor alpha; IL-6: interleukin-6; CRP: C-reactive protein; NO: nitric oxide; ET-1: endothelin-1.
Figure 2
Figure 2
The inflammatory-mediated HTN process, immune cells via different signaling pathways. The known routes, like signal transducer and activator of transcription -1, -3, and -5 (STAT), janus-associated kinases (JAK), domain containing phosphatase (SHP2) or extracellular signal related kinase and phosphatidylinositol-3-kinase (PIK3/AKT), depend on the specific interleukin production.

References

    1. WHO Mediacenter. Cardiovascular diseases (CVDs) fact sheets. 2017.
    1. World Health Organization. Global Health Oervatory (GHO) Data. 2015.
    1. Redwood H. Hypertension, society, and public policy. European Heart Journal. 2007;(Suppl 9):B13–B18. doi: 10.1093/eurheartj/sum003.
    1. Kranzhöfer R., Schmidt J., Pfeiffer C. A. H., Hagl S., Libby P., Kübler W. Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19(7):1623–1629. doi: 10.1161/01.ATV.19.7.1623.
    1. 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(12):1372–1378. doi: 10.1161/01.CIR.101.12.1372.
    1. Liu Y., Liu T., McCarron R. M., et al. Evidence for activation of endothelium and monocytes in hypertensive rats. American Journal of Physiology-Heart and Circulatory Physiology. 1996;270(6):H2125–H2131. doi: 10.1152/ajpheart.1996.270.6.H2125.
    1. Ross R. Atherosclerosis—an inflammatory disease. The New England Journal of Medicine. 1999;340(2):115–126. doi: 10.1056/NEJM199901143400207.
    1. Lia Q.-Z., Denga Q., Lia J.-Q., Yi G.-H. Valsartan reduces interleukin-1h secretion by peripheral blood mononuclear cells in patients with essential hypertension. Clinica Chimica Acta. 2005;355:131–136.
    1. Harrison D. G., Marvar P. J., Titze J. M. Vascular inflammatory cells in hypertension. Frontiers in Physiology. 2012;3, article 128 doi: 10.3389/fphys.2012.00128.
    1. Peng H., Yang X.-P., Carretero O. A., et al. Angiotensin II-induced dilated cardiomyopathy in Balb/c but not C57BL/6J mice. Experimental Physiology. 2011;96(8):756–764. doi: 10.1113/expphysiol.2011.057612.
    1. Bautista L. E., Vera L. M., Arenas I. A., Gamarra G. Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension. Journal of Human Hypertension. 2005;19(2):149–154. doi: 10.1038/sj.jhh.1001785.
    1. Tsoupras A., Lordan R., Zabetakis I. Inflammation, not cholesterol, is a cause of chronic disease. Nutrients. 2018;10(5):p. 604.
    1. Petitclerc E., Pouloee P. E., Marceau F. Rapid protein synthesis and turnover is involved in interleukin-l induced relaxation of the rabbit isolated mesenteric artery. Analysis of the arachidonate cascade. Journal of Pharmacology and Experimental Therapeutics. 1994;268:1419–1425.
    1. Angelovich T. A., Hearps A. C., Jaworowski A. Inflammation-induced foam cell formation in chronic inflammatory disease. Immunology & Cell Biology. 2015;93(8):683–693. doi: 10.1038/icb.2015.26.
    1. Agita A., Thaha M. Inflammation, immunity, and hypertension. The Indonesian Society of Internal Medicine. 2017;49(2)
    1. Taylor W. R. Hypertensive vascular disease and inflammation: mechanical and humoral mechanisms. Current Hypertension Reports. 1999;1(1):96–101. doi: 10.1007/s11906-999-0079-5.
    1. Teixeira B. C., Lopes A. L., Macedo R. C. O., et al. Inflammatory markers, endothelial function and cardiovascular risk. Jornal Vascular Brasileiro. 2014;13(2):108–115. doi: 10.1590/jvb.2014.054.
    1. Heitzer T., Schlinzig T., Krohn K., Meinertz T., Münzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation. 2001;104(22):2673–2678. doi: 10.1161/hc4601.099485.
    1. Mulvany M. J. Small artery remodelling in hypertension. Basic & Clinical Pharmacology & Toxicology. 2012;110(1):49–55. doi: 10.1111/j.1742-7843.2011.00758.x.
    1. Ferrario C. M., Strawn W. B. Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease. American Journal of Cardiology. 2006;98(1):121–128. doi: 10.1016/j.amjcard.2006.01.059.
    1. Finkel M. S., Oddis C. V., Jacob T. D., Watkins S. C., Hattler B. G., Simmons R. L. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science. 1992;257:387–389. doi: 10.1126/science.1631560.
    1. Didion S. Cellular and oxidative mechanisms associated with interleukin-6 signaling in the vasculature. International Journal of Molecular Sciences. 2017;18(12):p. 2563. doi: 10.3390/ijms18122563.
    1. Dikalov S. I., Dikalova A. E. Contribution of mitochondrial oxidative stress to hypertension. Current Opinion in Nephrology and Hypertension. 2016;25(2):73–80. doi: 10.1097/MNH.0000000000000198.
    1. Legein B., Temmerman L., Biessen E. A. L., Lutgens E. Inflammation and immune system interactions in atherosclerosis. Cellular and Molecular Life Sciences. 2013;70(20):3847–3869. doi: 10.1007/s00018-013-1289-1.
    1. Mroczko B., Groblewska M., Gryko M., Kedra B., Szmitkowski Diagnostic usefulness of serum interleukin 6 (IL-6) and C-reactive protein (CRP) in the dif-ferentiation between pancreatic cancer and chronic pancreatitis. Journal of Clinical Laboratory Analysis. 2010;24:256–261. doi: 10.1002/jcla.20395.
    1. Zhou L., Ivanov I. I., Spolski R. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nature Immunology. 2007;8(9):967–974. doi: 10.1038/ni1488.
    1. Lee D. L., Wilson J. L., Duan R., Hudson T., El-Marakby A. Peroxisome proliferator-activated receptor-α activation decreases mean arterial pressure, plasma interleukin-6, and COX-2 while increasing renal CYP4A expression in an acute model of DOCA-salt hypertension. PPAR Research. 2011:1–7.
    1. Sun L., Gao Y. H., Tian D. K., Zheng J. P., Zhu C. Y., Ke Y. Inflammation of different tissues in spontaneously hypertensive rats. Sheng Li Xue Bao. 2006;58:318–323.
    1. Bunting S., Gryglewski R., Moncada S., Vane J. R. Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac arteries and inhibits platelet aggregation. Prostaglandins. 1976;12(6):897–913. doi: 10.1016/0090-6980(76)90125-8.
    1. Bernatova I. Endothelial dysfunction in experimental models of arterial hypertension: cause or consequence? BioMed Research International. 2014;2014:14. doi: 10.1155/2014/598271.598271
    1. Tsoupras A. B., Iatrou C., Frangia C., Demopoulos C. A. The implication of platelet activating factor in cancer growth and metastasis: potent beneficial role of PAF-inhibitors and antioxidants. Infectious Disorders - Drug Targets. 2009;9(4):390–399. doi: 10.2174/187152609788922555.
    1. Kelesidis T., Papakonstantinou V., Detopoulou P., et al. The role of platelet-activating factor in chronic inflammation, immune activation, and comorbidities associated with HIV infection. AIDS Reviews. 2015;17(4):191–201.
    1. Sager H. B., Nahrendorf M. Inflammation: a trigger for acute coronary syndrome. European Journal of Nuclear Medicine and Molecular Imaging. 2016;60(2):185–193.
    1. Panoulas V. F., Douglas K. M. J., Milionis H. J., et al. Prevalence and associations of hypertension and its control in patients with rheumatoid arthritis. Rheumatology. 2007;46(9):1477–1482. doi: 10.1093/rheumatology/kem169.
    1. Neimann A. L., Shin D. B., Wang X., Margolis D. J., Troxel A. B., Gelfand J. M. Prevalence of cardiovascular risk factors in patients with psoriasis. Journal of the American Academy of Dermatology. 2006;55(5):829–835. doi: 10.1016/j.jaad.2006.08.040.
    1. Pierangeli S. S., Espinola R. G., Liu X., Harris E. N. Thrombogenic effects of antiphospholipid antibodies are mediated by intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and P-selectin. Circulation Research. 2001;88(2):245–250. doi: 10.1161/01.RES.88.2.245.
    1. Gokce N., Keaney J. F., Jr., Hunter L. M., et al. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. Journal of the American College of Cardiology. 2003;41(10):1769–1775. doi: 10.1016/S0735-1097(03)00333-4.
    1. Anderson T. J., Uehata A., Gerhard M. D., et al. Close relation of endothelial function in the human coronary and peripheral circulations. Journal of the American College of Cardiology. 1995;26(5):1235–1241. doi: 10.1016/0735-1097(95)00327-4.
    1. Heitzer T., Baldus S., Von Kodolitsch Y., Rudolph V., Meinertz T. Systemic endothelial dysfunction as an early predictor of adverse outcome in heart failure. Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25(6):1174–1179. doi: 10.1161/01.ATV.0000166516.52477.81.
    1. Ridker P. M., Rifai N., Stampfer M. J., Hennekens C. H. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000;101(15):1767–1772. doi: 10.1161/01.CIR.101.15.1767.
    1. Ioannidou E. Therapeutic modulation of growth factors and cytokines in regenerative medicine. Current Pharmaceutical Design. 2006;12(19):2397–2408. doi: 10.2174/138161206777699007.
    1. Ma J., Han H., Ma L., et al. The immunostimulatory effects of retinoblastoma cell supernatant on dendritic cells. Protein & Cell. 2014;5(4):307–316.
    1. Spinas E., Kritas S. K., Saggini A., et al. Role of mast cells in atherosclerosis: a classical inflammatory disease. International Journal of Immunopathology and Pharmacology. 2014;27(4):517–521. doi: 10.1177/039463201402700407.
    1. Singh M. V., Chapleau M. W., Harwani S. C., Abboud F. M. The immune system and hypertension. Immunologic Research. 2014;59(1–3):243–253. doi: 10.1007/s12026-014-8548-6.
    1. Ishibashi M., Hiasa K.-I., Zhao Q., et al. Critical role of monocyte chemoattractant protein-1 receptor CCR2 on monocytes in hypertension-induced vascular inflammation and remodeling. Circulation Research. 2004;94(9):1203–1210. doi: 10.1161/01.RES.0000126924.23467.A3.
    1. Mahmud A., Feely J. Arterial stiffness is related to systemic inflammation in essential hypertension. Hypertension. 2005;46(5):1118–1122. doi: 10.1161/01.hyp.0000185463.27209.b0.
    1. Guzik T. J., Touyz R. M. Oxidative stress, inflammation, and vascular aging in hypertension. Hypertension. 2017;70(4):660–667. doi: 10.1161/HYPERTENSIONAHA.117.07802.
    1. Laurent S., Boutouyrie P. The structural factor of hypertension: large and small artery alterations. Circulation Research. 2015;116(6):1007–1021. doi: 10.1161/CIRCRESAHA.116.303596.
    1. Manhiani M. M., Quigley J. E., Socha M. J., Motamed K., Imig J. D. IL6 suppression provides renal protection independent of blood pressure in a murine model of salt-sensitive hypertension. Kidney and Blood Pressure Research. 2007;30(4):195–202. doi: 10.1159/000104094.
    1. Norlander A. E., Madhur M. S., Harrison D. G. The immunology of hypertension. Journal of Experimental Medicine. 2018;215(1) doi: 10.1084/jem.20171773.
    1. Erion J. R., Wosiski-Kuhn M., Dey A., et al. Obesity elicits interleukin 1-mediated deficits in hippocampal synaptic plasticity. The Journal of Neuroscience. 2014;34(7):2618–2631. doi: 10.1523/jneurosci.4200-13.2014.
    1. Libby P., Ridker P. M., Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135–1143. doi: 10.1161/hc0902.104353.
    1. Welsh P., Grassia G., Botha S., Sattar N., Maffia P. Targeting inflammation to reduce cardiovascular disease risk: a realistic clinical prospect? British Journal of Pharmacology. 2017;174(22):3898–3913. doi: 10.1111/bph.13818.
    1. Andrzejczak D., Górska D., Czarnecka E. Influence of enalapril, quinapril and losartan on lipopolysaccharide (LPS)-induced serum concentrations of TNF-α, IL-1β, IL-6 in spontaneously hypertensive rats (SHR) Pharmacological Reports. 2007;59(4):437–446.
    1. White L. R., Juul R., Skaanes K. O., Aasly J. Cytokine enhancement of endothelin ET(B) receptor-mediated contraction in human temporal artery. European Journal of Pharmacology. 2000;406(1):117–122. doi: 10.1016/S0014-2999(00)00642-7.
    1. Kahlenberg J. M., Dubyak G. R. Differing caspase-1 activation states in monocyte versus macrophage models of IL-1β processing and release. Journal of Leukocyte Biology. 2004;76(3):676–684. doi: 10.1189/jlb.0404221.
    1. Cahill C. M., Rogers J. T. Interleukin (IL) 1β induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinase-dependent AKT/IκB kinase α pathway targeting activator protein-1. The Journal of Biological Chemistry. 2008;283(38):25900–25912. doi: 10.1074/jbc.M707692200.
    1. Mills K. H. G., Dungan L. S., Jones S. A., Harris J. The role of inflammasome-derived IL-1 in driving IL-17 responses. Journal of Leukocyte Biology. 2013;93(4):489–497. doi: 10.1189/jlb.1012543.
    1. Nemati F., Rahbar-Roshandel N., Hosseini F., Mahmoudian M., Shafiei M. Anti-inflammatory effects of anti-hypertensive agents: influence on interleukin-1β secretion by peripheral blood polymorphonuclear leukocytes from patients with essential hypertension. Clinical and Experimental Hypertension. 2011;33(2):69–76. doi: 10.3109/10641963.2010.496521.
    1. Krishnan S. M., Sobey C. G., Latz E., Mansell A., Drummond G. R. IL-1β and IL-18: inflammatory markers or mediators of hypertension? British Journal of Pharmacology. 2014;171(24):5589–5602. doi: 10.1111/bph.12876.
    1. Huang G., Niu T., Peng S., et al. Association between the interleukin-1β C(−511)T polymorphism and blood pressure in a Chinese hypertensive population. Immunology Letters. 2004;91(2-3):159–162. doi: 10.1016/j.imlet.2003.11.009.
    1. Francis S. E., Camp N. J., Dewberry R. M., et al. Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease. Circulation. 1999;99(7):861–866. doi: 10.1161/01.CIR.99.7.861.
    1. Lin R. C. Y., Morris B. J. Association analysis of polymorphisms at the interleukin-1 locus in essential hypertension. American Journal of Medical Genetics. 2002;107(4):311–316. doi: 10.1002/ajmg.10177.
    1. Pakistan Medical Research Council. National Health Survey of Pakistan 1990–94. Pakistan Medical Research Council, Network Publication Service: Islamabad, Pakistan, 1998.
    1. Khawaja M. R., Taj F., Saleheen D., et al. Association study of two interleukin-1 gene loci with essential hypertension in a Pakistani Pathan population. Journal of Human Hypertension. 2008;22(1):60–62. doi: 10.1038/sj.jhh.1002257.
    1. Yanagisawa A., Suzuki K., Kimura A., Ito Y., Hamajima N., Inoue T. Possible protective effect of serum β-carotene levels on the association between interleukin-1B C-31T polymorphism and hypertension in a Japanese population. Clinical Nutrition. 2009;28(2):198–202. doi: 10.1016/j.clnu.2009.01.020.
    1. Yang S. Exonic polymorphism (rs315952, Ser133Ser) of interleukin 1 receptor antagonist (IL1RN) is related to overweigh/obese with hypertension. Journal of Exercise Rehabilitation. 2014;10(5):332–336. doi: 10.12965/jer.140155.
    1. Qi J., Zhao X.-F., Yu X.-J., et al. Targeting interleukin-1 beta to suppress sympathoexcitation in hypothalamic paraventricular nucleus in dahl salt-sensitive hypertensive rats. Cardiovascular Toxicology. 2016;16(3):298–306. doi: 10.1007/s12012-015-9338-7.
    1. Zohlnhofer D., Brand K., Schipek K., Pogatsa-Murray G., Schomig A., Neumann F. J. Adhesion of monocyte very late antigen-4 to endothelial vascular cell adhesion molecule-1 induces interleukin-1β–dependent expression of interleukin-6 in endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20(2):353–359. doi: 10.1161/01.ATV.20.2.353.
    1. Kirii H., Niwa T., Yamada Y., et al. Lack of interleukin-1h decreases the severity of atherosclerosis in ApoE-deficient mice. Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:656.
    1. Barbieri M., Ferrucci L., Corsi A. M., et al. Is chronic inflammation a determinant of blood pressure in the elderly? American Journal of Hypertension. 2003;16(7):537–543. doi: 10.1016/S0895-7061(03)00861-6.
    1. Takahashi H., Nishimura M., Sakamoto M., Ikegaki I., Nakanishi T., Yoshimura M. Effects of interleukin-1beta on blood pressure, sympathetic nerve activity, and pituitary endocrine functions in anesthetized rats. American Journal of Hypertension. 1992;5:224–229.
    1. Krüttgen A., Rose-John S. Interleukin-6 in sepsis and capillary leakage syndrome. Journal of Interferon & Cytokine Research. 2012;32(2):60–65. doi: 10.1089/jir.2011.0062.
    1. Stenvinkel P., Barany P., Heimbürger O., Pecoits-Filho R., Lindholm B. Mortality, malnutrition, and atherosclerosis in ESRD: what is the role of interleukin-6? Kidney International. 2002;61:S103–S108. doi: 10.1046/j.1523-1755.61.s80.19.x.
    1. Hunter C. A., Jones S. A. IL-6 as a keystone cytokine in health and disease. Nature Immunology. 2015;16(5):448–457. doi: 10.1038/ni.3153.
    1. Heinrich P. C., Behrmann I., Haan S., Hermanns H. M., Müller-Newen G., Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochemical Journal. 2003;374:1–20. doi: 10.1042/BJ20030407.
    1. Acosta-Rodriguez E. V., Napolitani G., Lanzavecchia A., Sallusto F. Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nature Immunology. 2007;8(9):942–949. doi: 10.1038/ni1496.
    1. Woods A., Brull D. J., Humphries S. E., Montgomery H. E. Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. European Heart Journal. 2000;21(19):1574–1583. doi: 10.1053/euhj.1999.2207.
    1. Dong J., Fujii S., Goto D., et al. Increased expression of plasminogen activator inhibitor-1 by mediators of the acute phase response: a potential progenitor of vasculopathy in hypertensives. Hypertension Research. 2003;26(9):723–729. doi: 10.1291/hypres.26.723.
    1. Abbas A. K., Lichtman A. H. H., Pillai S. Cellular and Molecular Immunology. Philadelphia, PA, USA: Elsevier Health Sciences; 1994.
    1. Didion S. P. Cellular and oxidative mechanisms associated with interleukin-6 signaling in the vasculature. International Journal of Molecular Sciences. 2017;18(12):p. 2563. doi: 10.3390/ijms18122563.
    1. Bermudez E. A., Rifai N., Buring J., Manson J. E., Ridker P. M. Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women. Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22(10):1668–1673. doi: 10.1161/01.atv.0000029781.31325.66.
    1. Chamarthi B., Williams G. H., Ricchiuti V., et al. Inflammation and hypertension: the interplay of interleukin-6, dietary sodium, and the renin-angiotensin system in humans. American Journal of Hypertension. 2011;24(10):1143–1148. doi: 10.1038/ajh.2011.113.
    1. Silacci P., Dayer J.-M., Desgeorges A., Peter R., Manueddu C., Guernet P.-A. Interleukin (IL)-6 and its soluble receptor induce TIMP-1 expression in synoviocytes and chondrocytes, and block IL-1-induced collagenolytic activity. The Journal of Biological Chemistry. 1998;273(22):13625–13629. doi: 10.1074/jbc.273.22.13625.
    1. Mao S.-Q., Sun J.-H., Gu T.-L., Zhu F.-B., Yin F.-Y., Zhang L.-N. Hypomethylation of interleukin-6 (IL-6) gene increases the risk of essential hypertension: a matched case-control study. Journal of Human Hypertension. 2017;31(8):530–536. doi: 10.1038/jhh.2017.7.
    1. Gibas-Dorna M., Nowaki D., Piatek J. Plasma gherilin and interleukin-6 levels correlate with body mass index and arterial blood pressure in males with essentiaial hypertension. Journal of Physiology and Pharmacology. 2015;66(3):367–372.
    1. Lakoski S. G., Cushman M., Siscovick D. S., et al. The relationship between inflammation, obesity and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA) Journal of Human Hypertension. 2011;25(2):73–79. doi: 10.1038/jhh.2010.91.
    1. Naya M., Tsukamoto T., Morita K., et al. Plasma interleukin-6 and tumor necrosis factor-α can predict coronary endothelial dysfunction in hypertensive patients. Hypertension Research. 2007;30(6):541–548. doi: 10.1291/hypres.30.541.
    1. Finkel M. S., Oddis C. V., Jacob T. D., Watkins S. C., Hattler B. G., Simmons R. L. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science. 1992;257(5068):387–389. doi: 10.1126/science.1631560.
    1. Hirota H., Yoshida K., Kishimoto T., Taga T. Continuous activation of gp130, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. Proceedings of the National Acadamy of Sciences of the United States of America. 1995;92(11):4862–4866. doi: 10.1073/pnas.92.11.4862.
    1. Yan A. T., Yan R. T., Cushman M., et al. Relationship of interleukin-6 with regional and global left-ventricular function in asymptomatic individuals without clinical cardiovascular disease: insights from the multi-ethnic study of atherosclerosis. European Heart Journal. 2010;31(7):875–882. doi: 10.1093/eurheartj/ehp454.
    1. Janssen S. P. M., Gayan-Ramirez G., Van Den Bergh A., et al. Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats. Circulation. 2005;111(8):996–1005. doi: 10.1161/01.CIR.0000156469.96135.0D.
    1. Meléndez G. C., McLarty J. L., Levick S. P., Du Y., Janicki J. S., Brower G. L. Interleukin 6 mediates myocardial fibrosis, concentric hypertrophy, and diastolic dysfunction in rats. Hypertension. 2010;56(2):225–231. doi: 10.1161/HYPERTENSIONAHA.109.148635.
    1. Kobara M., Noda K., Kitamura M., et al. Antibody against interleukin-6 receptor attenuates left ventricular remodelling after myocardial infarction in mice. Cardiovascular Research. 2010;87(3):424–430. doi: 10.1093/cvr/cvq078.
    1. Lai N. C., Gao M. H., Tang E., et al. Pressure overload-induced cardiac remodeling and dysfunction in the absence of interleukin 6 in mice. Laboratory Investigation. 2012;92(11):1518–1526. doi: 10.1038/labinvest.2012.97.
    1. Sano M., Fukuda K., Kodama H., et al. Interleukin-6 family of cytokines mediate angiotensin II-induced cardiac hypertrophy in rodent cardiomyocytes. The Journal of Biological Chemistry. 2000;275(38):29717–29723. doi: 10.1074/jbc.M003128200.
    1. Bürger A., Benicke M., Deten A., Zimmer H. Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts. American Journal of Physiology-Heart and Circulatory Physiology. 2001;281(1):H14–H21. doi: 10.1152/ajpheart.2001.281.1.H14.
    1. Sterpetti A. V., Cucina A., Morena A. R., et al. Shear stress increases the release of interleukin-1 and interleukin-6 by aortic endothelial cells. Surgery. 1993;114(5):911–914.
    1. Michael W., Brands Amy K. L., Edward W. Interleukin-6 knockout prevents angiotensin II hypertension: role of renal vasoconstriction and JAK2/STAT3 activation. Hypertension. 2010;56(5):879–884.
    1. Lee D. L., Wilson J. L., Duan R., Hudson T., El-Marakby A. Peroxisome proliferator-activated receptor-α activation decreases mean arterial pressure, plasma interleukin-6, and COX-2 while increasing renal CYP4A expression in an acute model of DOCA-salt hypertension. PPAR Research. 2011;2011:7. doi: 10.1155/2011/502631.502631
    1. Zhang W., Wang W., Yu H., et al. Interleukin 6 underlies angiotensin II-induced hypertension and chronic renal damage. Hypertension. 2012;59(1):136–144. doi: 10.1161/HYPERTENSIONAHA.111.173328.
    1. Satou R., Gonzalez-Villalobos R. A., Miyata K., et al. Costimulation with angiotensin II and interleukin 6 augments angiotensinogen expression in cultured human renal proximal tubular cells. American Journal of Physiology-Renal Physiology. 2008;295(1):F283–F289. doi: 10.1152/ajprenal.00047.2008.
    1. Prins K. W., Archer S. L., Pritzker M., et al. Interleukin-6 is independently associated with right ventricular function in pulmonary arterial hypertension. The Journal of Heart and Lung Transplantation. 2018;37(3):376–384. doi: 10.1016/j.healun.2017.08.011.
    1. Gadonski G., LaMarca B. B. D., Sullivan E., Bennett W., Chandler D., Granger J. P. Hypertension produced by reductions in uterine perfusion in the pregnant rat: role of interleukin 6. Hypertension. 2006;48(4):711–716. doi: 10.1161/01.HYP.0000238442.33463.94.
    1. Maston L. D., Jones D. T., Giermakowska W., et al. Interleukin-6 trans-signaling contributes to chronic hypoxia-induced pulmonary hypertension. Pulmonary Circulation. 2018;8(3) doi: 10.1177/2045894018780734.
    1. Maston L. D., Jones D. T., Giermakowska W., et al. Central role of T helper 17 cells in chronic hypoxia-induced pulmonary hypertension. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2017;312(5):L609–L624. doi: 10.1152/ajplung.00531.2016.
    1. Samuelsson A., Alexanderson C., Mölne J., Haraldsson B., Hansell P., Holmäng A. Prenatal exposure to interleukin-6 results in hypertension and alterations in the renin-angiotensin system of the rat. The Journal of Physiology. 2006;575(3):855–867. doi: 10.1113/jphysiol.2006.111260.
    1. Giovani Gadonski B., Babbette D., LaMarca. Hypertension produced by reductions in uterine perfusion in the pregnant rat. Hypertension. 2006;48:711–716.
    1. Benyo D. F., Smarason A., Redman C. W. G., Sims C., Conrad K. P. Expression of inflammatory cytokines in placentas from women with preeclampsia. The Journal of Clinical Endocrinology & Metabolism. 2001;86(6):2505–2512. doi: 10.1210/jc.86.6.2505.
    1. González G. E., Rhaleb N. E., D'Ambrosio M. A., et al. Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunction without affecting blood pressure in angiotensin II-high salt-induced hypertension. Journal of Hypertension. 2015;33(1):144–152. doi: 10.1097/HJH.0000000000000358.
    1. Banerjee I., Fuseler J. W., Intwala A. R., Baudino T. A. IL-6 loss causes ventricular dysfunction, fibrosis, reduced capillary density, and dramatically alters the cell populations of the developing and adult heart. American Journal of Physiology-Heart and Circulatory Physiology. 2009;296(5):H1694–H1704. doi: 10.1152/ajpheart.00908.2008.
    1. IL6R Genetics Consortium Emerging Risk Factors Collaboration, Sarwar N., Butterworth A. S., et al. Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. The Lancet. 2012;379:1205–1213. doi: 10.1016/s0140-6736(11)61931-4.
    1. Deloukas P., Kanoni S., Willenborg C. Large-scale association analysis identifies new risk loci for coronary artery disease. Nature Genetics. 2013;45(1):25–33. doi: 10.1038/ng.2480.
    1. Nakajima T., Ota N., Yoshida H., Watanabe S., Suzuki T., Emi M. Allelic variants in the interleukin-6 gene and essential hypertension in Japanese women. Genes & Immunity. 1999;1(2):115–119. doi: 10.1038/sj.gene.6363642.
    1. Tong Y., Wang Z., Geng Y., et al. The association of functional polymorphisms of IL-6 gene promoter with ischemic stroke: Analysis in two Chinese populations. Biochemical and Biophysical Research Communications. 2010;391(1):481–485. doi: 10.1016/j.bbrc.2009.11.084.
    1. Basso F., Lowe G. D., Rumley A., McMahon A. D., Humphries S. E. Interleukin-6 - 174G>Cpolymorphism and risk of coronary heart disease in West of Scotland coronary prevention study (WOSCOPS) Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:599–604.
    1. Pola R., Flex A., Gaetani E., Pola P., Bernabei R. The -174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population. Journal of Human Hypertension. 2002;16(9):637–640. doi: 10.1038/sj.jhh.1001462.
    1. Losito A., Kalidas K., Santoni S., Jeffery S. Association of interleukin-6—174G/C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients. Kidney International. 2003;64(2):616–622. doi: 10.1046/j.1523-1755.2003.00119.x.
    1. Grocott H. P., White W. D., Morris R. W., et al. Genetic polymorphisms and the risk of stroke after cardiac surgery. Stroke. 2005;36(9):1854–1858. doi: 10.1161/01.STR.0000177482.23478.dc.
    1. Timasheva Y. R., Nasibullin T. R., Zakirova A. N., Mustafina O. E. Association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension in Tatars from Russia. Biochemical Genetics. 2008;46(1-2):64–74. doi: 10.1007/s10528-007-9130-x.
    1. Elsaid A., Abdel-Aziz A. F., Elmougy R. Association of polymorphisms G(-174)C in IL-6 gene and G(-1082)A in IL-10 gene with traditional cardiovascular risk factors in patients with coronary artery disease. Indian Journal of Biochemistry & Biophysics. 2014;51:282–292.
    1. Brull D. J., Montgomery H. E., Sanders J., et al. Interleukin-6 gene -174G > C and -572G > C promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21(9):1458–1463. doi: 10.1161/hq0901.094280.
    1. Ma H., Sun G., Wang W. Association between interleukin-6 572 C>G and -174 G>C polymorphisms and hypertension. Medicine. 2016;95(2):p. e2416.
    1. Jiang C. Q., Lam T. H., Liu B., et al. Interleukin-6 receptor gene polymorphism modulates interleukin-6 levels and the metabolic syndrome: GBCS-CVD. Obesity. 2010;18(10):1969–1974. doi: 10.1038/oby.2010.31.
    1. Chen H., Shifang D., Liu X., Liu J., Yun W., Xiayin W. Association of interleukin-6 genetic polymorphisms and environment factors interactions with coronary artery disease in a chinese han population. Clinical and Experimental Hypertension. 2018;40(6):514–517. doi: 10.1080/10641963.2017.1403618.
    1. Li J., Song J., Jiang M.-H., et al. Interleukin-6 promoter polymorphisms and susceptibility to atrial fibrillation in Elderly Han Chinese patients with essential hypertension. Journal of Interferon & Cytokine Research. 2012;32(11):542–547. doi: 10.1089/jir.2012.0033.
    1. Seropian I. M., Toldo S., van Tassell B. W., Abbate A. Anti-inflammatory strategies for ventricular remodeling following St-segment elevation acute myocardial infarction. Journal of the American College of Cardiology. 2014;63(16):1593–1603. doi: 10.1016/j.jacc.2014.01.014.
    1. Iwakura Y., Ishigame H. The IL-23/IL-17 axis in inflammation. The Journal of Clinical Investigation. 2006;116(5):1218–1222. doi: 10.1172/JCI28508.
    1. Harrington L. E., Hatton R. D., Mangan P. R., et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature Immunology. 2005;6(11):1123–1132. doi: 10.1038/ni1254.
    1. Lexberg M. H., Taubner A., Förster A., et al. Th memory for interleukin-17 expression is stable in vivo. European Journal of Immunology. 2008;38(10):2654–2664. doi: 10.1002/eji.200838541.
    1. Erbel C., Dengler T. J., Wangler S., et al. Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability. Basic Research in Cardiology. 2011;106(1):125–134. doi: 10.1007/s00395-010-0135-y.
    1. Yan X., Shichita T., Katsumata Y., et al. Deleterious effect of the IL-23/IL-17A axis and γδT cells on left ventricular remodeling after myocardial infarction. Journal of the American Heart Association. 2012;1(5) doi: 10.1161/jaha.112.004408.e004408
    1. Singh M. V., Cicha M. Z., Kumar S., et al. Abnormal CD161 + immune cells and retinoic acid receptor–related orphan receptor γt–mediate enhanced IL-17F expression in the setting of genetic hypertension. The Journal of Allergy and Clinical Immunology. 2017;140(3):809–821. doi: 10.1016/j.jaci.2016.11.039.
    1. Von Vietinghoff S., Ley K. Interleukin 17 in vascular inflammation. Cytokine & Growth Factor Reviews. 2010;21(6):463–469. doi: 10.1016/j.cytogfr.2010.10.003.
    1. Cheng X., Yu X., Ding Y., et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clinical Immunology. 2009;127:89–97. doi: 10.1016/j.clim.2009.09.015.
    1. Meena S., Madhur Heinrich E., Louise A. Interleukin 17 promotes angiotensin II–induced hypertension and vascular dysfunction. Hypertension. 2010;55:500–507.
    1. Rahmati Z., Amirzargar A. A., Saadati S., et al. Association of levels of interleukin 17 and T-helper 17 count with symptom severity and etiology of chronic heart failure: a case-control study. Croatian Medical Journal. 2018;59(4):139–148. doi: 10.3325/cmj.2018.59.139.
    1. Wang Z., Shi W., Liang X., Wang W., Liang J. Association of interleukin 17 / angiotensin II with refractory hypertension risk in hemodialysis patients. African Health Sciences. 2016;16(3):766–771. doi: 10.4314/ahs.v16i3.17.
    1. Chung B. H., Kim K. W., Sun I. O., et al. Increased interleukin-17 producing effector memory T cells in the end-stage renal disease patients. Immunology Letters. 2012;141(2):181–189. doi: 10.1016/j.imlet.2011.10.002.
    1. Krebs C. F., Lange S., Niemann G., et al. Deficiency of the interleukin 17/23 axis accelerates renal injury in mice with deoxycorticosterone acetate+angiotensin II-induced hypertension. Hypertension. 2014;63(3):565–571. doi: 10.1161/HYPERTENSIONAHA.113.02620.
    1. Saleh M. A., Allison E., Madhur S. M. Inhibition of interleukin-17a, but not interleukin-17F, signaling lowers blood pressure, and reduces end-organ inflammation in angiotensin II–induced hypertension. JACC: Basic to Translational Science. 2016;1:606–616.
    1. Buemi M., Marino D., Floccari F., et al. Effect of interleukin 8 and ICAM-1 on calcium-dependent outflow of K + in erythrocytes from subjects with essential hypertension. Current Medical Research and Opinion. 2004;20(1):19–24. doi: 10.1185/030079903125002720.
    1. Bergholdt R., Ghandil P., Johannesen J., et al. Genetic and functional evaluation of an interleukin-12 polymorphism (IDDM18) in families with type 1 diabetes. Journal of Medical Genetics. 2004;41(4):p. e39. doi: 10.1136/jmg.2003.010454.
    1. Hoong S. L., Lip G. Y. H. Interleukin-15 in hypertension: Further insights into inflammation and vascular disease. American Journal of Hypertension. 2005;18(8):1017–1018. doi: 10.1016/j.amjhyper.2005.03.742.
    1. Kaibe M., Ohishi M., Ito N., et al. Serum interleukin-15 concentration in patients with essential hypertension. American Journal of Hypertension. 2005;18(8):1019–1025. doi: 10.1016/j.amjhyper.2005.02.014.
    1. Gracie J. A., Robertson S. E., McInnes I. B. Interleukin-18. Journal of Leukocyte Biology. 2003;73(2):213–224. doi: 10.1189/jlb.0602313.
    1. Elbim C., Guichard C., Dang P. M., et al. Interleukin-18 primes the oxidative burst of neutrophils in response to formyl-peptides: role of cytochrome b558 translocation and n-formyl peptide receptor endocytosis. Clinical and Vaccine Immunology. 2005;12(3):436–446. doi: 10.1128/CDLI.12.3.436-446.2005.
    1. Hernesniemi J. A., Karhunen P. J., Oksala N., et al. Interleukin 18 gene promoter polymorphism: a link between hypertension and pre-hospital sudden cardiac death: the helsinki sudden death study. European Heart Journal. 2009;30(23):2939–2946. doi: 10.1093/eurheartj/ehp316.
    1. Bis J. C., Heckbert S. R., Smith N. L., et al. Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke. Atherosclerosis. 2008;198(1):166–173. doi: 10.1016/j.atherosclerosis.2007.09.031.
    1. Blankenberg S., Luc G., Ducimetière P., et al. Interleukin-18 and the risk of coronary heart disease in european men: the prospective epidemiological study of myocardial infarction (PRIME) Circulation. 2003;108(20):2453–2459. doi: 10.1161/01.CIR.0000099509.76044.A2.
    1. Schett G., Elewaut D., McInnes I. B., Dayer J.-M., Neurath M. F. How cytokine networks fuel inflammation: toward a cytokine-based disease taxonomy. Nature Medicine. 2013;19(7):822–824. doi: 10.1038/nm.3260.
    1. Akbari H., Asadikaram G., Jafari A., et al. Atorvastatin, losartan and captopril may upregulate IL-22 in hypertension and coronary artery disease; the role of gene polymorphism. Life Sciences. 2018;207:525–531. doi: 10.1016/j.lfs.2018.07.005.
    1. Arend W. P., Palmer G., Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunological Reviews. 2008;223(1):20–38. doi: 10.1111/j.1600-065X.2008.00624.x.
    1. Ghali R., Altara R., Louch W. E., et al. IL-33 (interleukin 33)/sST2 axis in hypertension and heart failure. Hypertension. 2018;72(4):818–828. doi: 10.1161/HYPERTENSIONAHA.118.11157.
    1. Miguez J. S. G., Dela Justina V., Bressan A. F. M., et al. O-Glycosylation with O-linked β-N-acetylglucosamine increases vascular contraction: possible modulatory role on Interleukin-10 signaling pathway. Life Sciences. 2018;209:78–84. doi: 10.1016/j.lfs.2018.07.058.
    1. Girndt M., Köhler H. Interleukin-10: an update on its relevance for cardiovascular risk. Nephrol Dial Transplant. 2003;18:1976–1979.
    1. Zemse S. M., Chiao C. W., Hilgers R. H. P., Webb R. C. Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-α on the endothelium of murine aorta. American Journal of Physiology-Heart and Circulatory Physiology. 2010;299(4):H1160–H1167. doi: 10.1152/ajpheart.00763.2009.
    1. Yang Z. F., Ngai P., Lau C. K., et al. Induction of long-term liver allograft survival by delayed immunosuppression is dependent on interleukin-10. Liver Transplantation. 2007;13(4):571–578. doi: 10.1002/lt.21091.
    1. Lima V. V., Zemse S. M., Chiao C.-W., et al. Interleukin-10 limits increased blood pressure and vascular RhoA/Rho-kinase signaling in angiotensin II-infused mice. Life Sciences. 2016;145:137–143. doi: 10.1016/j.lfs.2015.12.009.
    1. Mulligan M. S., Warner R. L., McDuffie J. E., Bolling S. F., Sarma J. V., Ward P. A. Regulatory role of Th-2 cytokines, IL-10 and IL-4, in cardiac allograft rejection. Experimental and Molecular Pathology. 2000;69(1):1–9. doi: 10.1006/exmp.2000.2304.
    1. Chatterjee P., Chiasson V. L., Seerangan G., et al. Cotreatment with interleukin 4 and interleukin 10 modulates immune cells and prevents hypertension in pregnant mice. American Journal of Hypertension. 2015;28(1):135–142. doi: 10.1093/ajh/hpu100.
    1. van der Meij E., Koning G. G., Vriens P. W., et al. A clinical evaluation of statin pleiotropy: statins selectively and dose-dependently reduce vascular inflammation. PLoS ONE. 2013;8(1)e53882
    1. Grundy S. M., Stone N. J., Bailey A. L., et al. Cholesterol clinical practice guidelines. American College of Cardiology. 2018;1097(18):39033–39038.
    1. Sepehri Z., Masoumi M., Ebrahimi N., et al. Atorvastatin, losartan and captopril lead to upregulation of TGF-β, and downregulation of IL-6 in coronary artery disease and hypertension. PLoS ONE. 2016;11(12) doi: 10.1371/journal.pone.0168312.e0168312
    1. Rizzo M., Montalto G., Banach M., et al. The effects of statins on blood pressure: current knowledge and future perspectives. Archives of Medical Science. 2012;8(1):1–3. doi: 10.5114/aoms.2012.27270.
    1. Shuiping Z., Quanzhong L., Ling L., et al. Simvastatin reduces interleukin-1β secretion by peripheral blood mononuclear cells in patients with essential hypertension. Clinica Chimica Acta. 2004;344(1-2):195–200.
    1. Owczarek J., Jasiñska M., Wejman I., Kurczewska U., Orszulak-Michalak D. Effects of 4-week administration of simvastatin in different doses on heart rate and blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats. Archives of Medical Science. 2012;8(1):17–21. doi: 10.5114/aoms.2012.27275.
    1. Drapala A., Aleksandrowicz M., Zera T., et al. The effect of simvastatin and pravastatin on arterial blood pressure, baroreflex, vasoconstrictor, and hypertensive effects of angiotensin II in Sprague-Dawley rats. Journal of the American Society of Hypertension. 2014;8(12):863–871. doi: 10.1016/j.jash.2014.09.008.
    1. Ledingham J. M., Laverty R. Effect of simvastatin given alone and in combination with valsartan or enalapril on blood pressure and the structure of mesenteric resistance arteries and the basilar artery in the genetically hypertensive rat model. Clinical and Experimental Pharmacology and Physiology. 2005;32(1-2):76–85. doi: 10.1111/j.1440-1681.2004.04162.x.
    1. Zhao J., Cheng Q., Liu Y., Yang G., Wang X. Atorvastatin alleviates early hypertensive renal damage in spontaneously hypertensive rats. Biomedicine & Pharmacotherapy. 2019;109:602–609. doi: 10.1016/j.biopha.2018.10.165.
    1. Drapala A., Sikora M., Ufnal M., et al. Statins, the renin-angiotensin-aldosterone system and hypertension - A tale of another beneficial effect of statins. JRAAS - Journal of the Renin-Angiotensin-Aldosterone System. 2014;15(3):250–258. doi: 10.1177/1470320314531058.
    1. Andrzejczak D., Górska D., Czarnecka E. Influence of amlodipine and atenolol on lipopolysaccharide (LPS)-induced serum concentrations of TNF-α, IL-1β, IL-6 in spontaneously hypertensive rats (SHR) Pharmacological Reports. 2006;58(5):711–719.
    1. Zhang J., Rudemiller N. P., Patel M. B., et al. Interleukin-1 receptor activation potentiates salt reabsorption in angiotensin II-induced hypertension via the NKCC2 Co-transporter in the nephron. Cell Metabolism. 2016;23(2):360–368. doi: 10.1016/j.cmet.2015.11.013.
    1. Lu J., Hao J., Du H., et al. Amlodipine and atorvastatin improved hypertensive cardiac remodeling through regulation of MMPs/TIMPs in SHR rats. Cellular Physiology and Biochemistry. 2016;39(1):47–60. doi: 10.1159/000445604.
    1. Mattson D. L., James L., Berdan E. A., Meister C. J. Immune suppression attenuates hypertension and renal disease in the Dahl salt-sensitive rat. Hypertension. 2006;48(1):149–156. doi: 10.1161/01.HYP.0000228320.23697.29.
    1. Farah R., Khamisy-Farah R., Shurtz-Swirski R., et al. Calcium channel blocker effect on insulin resistance and inflammatory markers in essential hypertension patients. International Angiology. 2013;32(1):85–93.
    1. de Miguel C., Das S., Lund H., Mattson D. L. T lymphocytes mediate hypertension and kidney damage in Dahl salt-sensitive rats. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2010;298(4):R1136–R1142. doi: 10.1152/ajpregu.00298.2009.
    1. Boesen E. I., Williams D. L., Pollock J. S., Pollock D. M. Immunosuppression with mycophenolate mofetil attenuates the development of hypertension and albuminuria in deoxycorticosterone acetate-salt hypertensive rats. Clinical and Experimental Pharmacology and Physiology. 2010;37(10):1016–1022. doi: 10.1111/j.1440-1681.2010.05428.x.
    1. Villarroel M. C, Hidalgo M., Jimeno A. Mycophenolate mofetil: an update. Drugs Today (Barc) 2009;45(7):521–532. doi: 10.2165/00128415-200912640-00033.
    1. Rodríguez-Iturbe B., Quiroz Y., Nava M., et al. Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats. American Journal of Physiology-Renal Physiology. 2002;282(2):F191–F201. doi: 10.1152/ajprenal.0197.2001.
    1. Moes A. D., Severs D., Verdonk K., et al. Mycophenolate mofetil attenuates DOCA-salt hypertension: effects on vascular tone. Frontiers in Physiology. 2018;9:p. 578. doi: 10.3389/fphys.2018.00578.
    1. Taylor E. B., Ryan M. J. Immunosuppression with mycophenolate mofetil attenuates hypertension in an experimental model of autoimmune disease. Journal of the American Heart Association. 2017;6(3) doi: 10.1161/JAHA.116.005394.e005394
    1. González G. E., Rhaleb N.-E., D'Ambrosio M. A., et al. Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunctionwithout affecting blood pressure in angiotensin II-high salt-induced hypertension. Journal of Hypertension. 2015;33(1):144–152. doi: 10.1097/HJH.0000000000000358.
    1. Frieder J., Kivelevitch D., Menter A. Secukinumab: a review of the anti-IL-17A biologic for the treatment of psoriasis. Therapeutic Advances in Chronic Disease. 2018;9(1):5–21. doi: 10.1177/2040622317738910.
    1. Hernández-Sánchez J., Harlow L., Church C., et al. Clinical trial protocol for TRANSFORM-UK: a therapeutic open-label study of tocilizumab in the treatment of pulmonary arterial hypertension. Pulmonary Circulation. 2017;8(1) doi: 10.1177/2045893217735820.
    1. Cornelius D. C., Hogg J. P., Scott J., et al. Administration of interleukin-17 soluble receptor C supresses TH17 cells, oxidative stress, and hypertension in response to placental ischemia during pregnancy. Hypertension. 2013;62(6):1068–1073. doi: 10.1161/HYPERTENSIONAHA.113.01514.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera