Abstract
Low grade inflammation may have a key role in the pathogenesis of hypertension and cardiovascular disease. Several studies showed that both innate and adaptive immune systems may be involved, being T cells the most important players. Particularly, the balance between Th1 effector lymphocytes and Treg lymphocytes may be crucial for blood pressure elevation and related organ damage development. In the presence of a mild elevation of blood pressure, neo-antigens are produced. Activated Th1 cells may then contribute to the persistent elevation of blood pressure by affecting vasculature, kidney and perivascular fat. On the other hand, Tregs represent a lymphocyte subpopulation with an anti-inflammatory role, being their activity crucial for the maintenance of cardiovascular homeostasis. Indeed, Tregs were demonstrated to be able to protect from blood pressure elevation and from the development of organ damage, including micro and macrovascular alterations, in different animal models of genetic or experimental hypertension. In the vasculature, inflammation leads to vascular remodeling through cytokine activity, smooth muscle cell proliferation and oxidative stress. It is also known that a consistent part of ischemia-reperfusion-induced acute kidney injury is mediated by inflammatory infiltration and that Treg cell infusion have a protective role. Also the central nervous system has an important role in the maintenance of cardiovascular homeostasis. In conclusion, hypertension development involves chronic inflammatory process. Knowledge of cellular and molecular players in the progression of hypertension has dramatically improved in the last decade, by assessing the central role of innate and adaptive immunity cells and proinflammatory cytokines driving the development of target organ damage. The new concept of role of immunity, especially implicating T lymphocytes, will eventually allow discovery of new therapeutic targets that may improve outcomes in hypertension and cardiovascular or renal disease in humans and uncover an entirely novel approach in the treatment of hypertension and vascular disease.
Similar content being viewed by others
References
Tracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009;9(6):418–28 Review.
Intengan HD, Schiffrin EL. Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension. 2001;38:581–7.
Leibowitz A, Schiffrin EL. Immune mechanisms in hypertension. Curr Hypertens Rep. 2011;13:465–72.
Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, Vinh A, Weyand CM. Inflammation, immunity, and hypertension. Hypertension. 2011;57:132–40.
Harrison DG, Vinh A, Lob H, Madhur MS. Role of the adaptive immune system in hypertension. Curr Opin Pharmacol. 2010;10:203–7.
Schiffrin EL. T lymphocytes: a role in hypertension? Curr Opin Nephrol Hypertens. 2010;19:181–6.
Schiffrin EL. The immune system role in hypertension. Can J Cardiol. 2013;29:543–8.
Mai J, Wang H, Yang X. Th 17 cells interplay with Foxp3+ Tregs in regulation of inflammation and autoimmunity. Front Biosci. 2010;15:986–1006.
Kassan M, Wecker A, Kadowitz P, Trebak M, Matrougui K. CD4+CD25+Foxp3 regulatory T cells and vascular dysfunction in hypertension. J Hypertens. 2013;31:1939–43.
Taleb S, Tedgui A, Mallat Z. Regulatory T-cell immunity and its relevance to atherosclerosis. J Intern Med. 2008;263:489–99.
Schiffrin EL. Immune mechanisms in hypertension and vascular injury. Clin Sci (Lond). 2014;126:267–74.
Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, Watson AD, Lusis AJ. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation. 1995;91:2488–96.
De Ciuceis C, Amiri F, Brassard P, Endemann DH, Touyz RM, Schiffrin EL. Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of Ang II-infused macrophage colony-stimulating factor-deficient mice: evidence for a role in inflammation in Ang II-induced vascular injury. Arterioscler Thromb Vasc Biol. 2005;25:2106–13.
Ko EA, Amiri F, Pandey NR, Javeshghani D, Leibovitz E, Touyz RM, Schiffrin EL. Resistance artery remodeling in deoxycorticosterone acetate-salt hypertension is dependent on vascular inflammation: evidence from m-CSF-deficient mice. Am J Physiol Heart Circ Physiol. 2007;292:H1789–95.
Guzik TJ, Hoch NE, Brown KA, et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007;204:2449–60.
Madhur MS, Harrison DG. Senescent T cells and hypertension: new ideas about old cells. Hypertension. 2013;62:13–5.
Virdis A, Schiffrin EL. Vascular inflammation: a role in vascular disease in hypertension? Curr Opin Nephrol Hypertens. 2003;12:181–7.
Lob HE, Marvar PJ, Guzik TJ, Sharma S, McCann LA, Weyand C, Gordon FJ, Harrison DG. Induction of hypertension and peripheral inflammation by reduction of extracellular superoxide dismutase in the central nervous system. Hypertension. 2010;55:277–83.
Kinsey GR, Sharma R, Huang L, Li L, Vergis AL, Ye H, Ju ST, Okusa MD. Regulatory T cells suppress innate immunity in kidney ischemia-reperfusion injury. J Am Soc Nephrol. 2009;20:1744–53.
Viel EC, Lemarié CA, Benkirane K, Paradis P, Schiffrin EL. Immune regulation and vascular inflammation in genetic hypertension. Am J Physiol Heart Circ Physiol. 2010;298:H938–44.
Barhoumi T, Kasal DA, Li MW, Shbat L, Laurant P, Neves MF, Paradis P, Schiffrin EL. T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury. Hypertension. 2011;57(3):469–76.
Shao J, Nangaku M, Miyata T, Inagi R, Yamada K, Kurokawa K, Fujita T. Imbalance of T-cell subsets in angiotensin II-infused hypertensive rats with kidney injury. Hypertension. 2003;42:31–8.
Crowley SD, Song YS, Lin EE, Griffiths R, Kim HS, Ruiz P. Lymphocyte responses exacerbate angiotensin II-dependent hypertension. Am J Physiol Regul Integr Comp Physiol. 2010;298:R1089–97.
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;55:500–7.
Kvakan H, Kleinewietfeld M, Qadri F, Park JK, Fischer R, Schwarz I, Rahn HP, Plehm R, Wellner M, Elitok S, Gratze P, Dechend R, Luft FC, Muller DN. Regulatory T cells ameliorate angiotensin II-induced cardiac damage. Circulation. 2009;119:2904–12.
Kassan M, Galan M, Partyka M, Trebak M, Matrougui K. Interleukin-10 released by CD4+CD25+ natural regulatory T cells improves microvascular endothelial function through inhibition of NADPH oxidase activity in hypertensive mice. Arterioscler Thromb Vasc Biol. 2011;11:2534–42.
Tinsley JH, South S, Chiasson VL, Mitchell BM. Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats. Am J Physiol Regul Integr Comp Physiol. 2010;298:R713–9.
Marvar PJ, Thabet SR, Guzik TJ, Lob HE, McCann LA, Weyand C, Gordon FJ. Harrison DG Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension. Circ Res. 2010;107:263–70.
Schiffrin EL. Immune mechanisms in hypertension: how do T-regulatory lymphocytes fit in? J Hypertens. 2013;31:1944–5.
Youn JC, Yu HT, Lim BJ, Koh MJ, Lee J, Chang DY, Choi YS, Lee SH, Kang SM, Jang Y, Yoo OJ, Shin EC, Park S. Immunosenescent CD8+ T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension. Hypertension. 2013;62:126–33.
De Miguel C, Das S, Lund H, Mattson DL. T lymphocytes mediate hypertension and kidney damage in Dahl salt-sensitive rats. Am J Physiol Regul Integr Comp Physiol. 2010;298(4):R1136–42.
Crowley SD, Frey CW, Gould SK, Griffiths R, Ruiz P, Burchette JL, Howell DN, Makhanova N, Yan M, Kim HS, Tharaux PL, Coffman TM. Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension. Am J Physiol Renal Physiol. 2008;295:F515–24.
Rodríguez-Iturbe B, Pons H, Quiroz Y, Gordon K, Rincón J, Chávez M, Parra G, Herrera-Acosta J, Gómez-Garre D, Largo R, Egido J, Johnson RJ. Mycophenolate mofetil prevents salt-sensitive hypertension resulting from angiotensin II exposure. Kidney Int. 2001;59:2222–32.
Venegas-Pont M, Manigrasso MB, Grifoni SC, LaMarca BB, Maric C, Racusen LC, Glover PH, Jones AV, Drummond HA, Ryan MJ. Tumor necrosis factor-alpha antagonist etanercept decreases blood pressure and protects the kidney in a mouse model of systemic lupus erythematosus. Hypertension. 2010;56:643–9.
Elmarakby AA, Quigley JE, Imig JD, Pollock JS, Pollock DM. TNF-alpha inhibition reduces renal injury in DOCA-salt hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2008;294:R76–83.
Seaberg EC, Muñoz A, Lu M, Detels R, Margolick JB, Riddler SA, Williams CM, Phair JP, Multicenter AIDS Cohort Study. Association between highly active antiretroviral therapy and hypertension in a large cohort of men followed from 1984 to 2003. AIDS. 2005;19:953–60.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
De Ciuceis, C., Rossini, C., La Boria, E. et al. Immune Mechanisms in Hypertension. High Blood Press Cardiovasc Prev 21, 227–234 (2014). https://doi.org/10.1007/s40292-014-0040-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40292-014-0040-9