Hypertension is a leading cause of worldwide morbidity and mortality, leading to stroke, myocardial infarction, vascular disease, and chronic kidney disease. Emerging evidence from our laboratory and others indicates that hypertension is an inflammatory process in which T cells and T cell-derived cytokines play a central role. Despite this evidence, there are currently no treatments for hypertension that target the immune system. We were the first to demonstrate a critical role for the pro-inflammatory cytokine, interleukin 17A (IL17A), in angiotensin II induced hypertension and vascular dysfunction. When given angiotensin II, mice lacking IL17A have reduced blood pressure and preserved vascular function compared to normal mice. Recent data demonstrates that salt can directly influence naive T cells to differentiate into IL17 producing cells. How T cells can sense and respond to salt is unknown. My current research focus is how T cells and T cell-derived cytokines promote hypertension and renal/vascular dysfunction.

Publications

Featured publications

  1. A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage. Norlander AE, Saleh MA, Pandey AK, Itani HA, Wu J, Xiao L, Kang J, Dale BL, Goleva SB, Laroumanie F, Du L, Harrison DG, Madhur MS (2017) JCI Insight 2(13)
    › Primary publication · 28679951 (PubMed) · PMC5499362 (PubMed Central)
  2. Inflammatory cytokines regulate renal sodium transporters: how, where, and why? Norlander AE, Madhur MS (2017) Am J Physiol Renal Physiol 313(2): F141-F144
    › Primary publication · 28404590 (PubMed)
  3. Inhibition of Interleukin 17-A but not Interleukin-17F Signaling Lowers Blood Pressure and Reduces End-organ Inflammation in Angiotensin II-induced Hypertension. Saleh MA, Norlander AE, Madhur MS (2016) JACC Basic Transl Sci 1(7): 606-616
    › Primary publication · 28280792 (PubMed) · PMC5337944 (PubMed Central)
  4. Intracellular Staining and Flow Cytometry to Identify Lymphocyte Subsets within Murine Aorta, Kidney and Lymph Nodes in a Model of Hypertension. Laroumanie F, Dale BL, Saleh MA, Madhur MS (2017) J Vis Exp (119)
    › Primary publication · 28190037 (PubMed)
  5. Activation of Human T Cells in Hypertension: Studies of Humanized Mice and Hypertensive Humans. Itani HA, McMaster WG, Saleh MA, Nazarewicz RR, Mikolajczyk TP, Kaszuba AM, Konior A, Prejbisz A, Januszewicz A, Norlander AE, Chen W, Bonami RH, Marshall AF, Poffenberger G, Weyand CM, Madhur MS, Moore DJ, Harrison DG, Guzik TJ (2016) Hypertension 68(1): 123-32
    › Primary publication · 27217403 (PubMed) · PMC4900908 (PubMed Central)
  6. Interleukin-17A Regulates Renal Sodium Transporters and Renal Injury in Angiotensin II-Induced Hypertension. Norlander AE, Saleh MA, Kamat NV, Ko B, Gnecco J, Zhu L, Dale BL, Iwakura Y, Hoover RS, McDonough AA, Madhur MS (2016) Hypertension 68(1): 167-74
    › Primary publication · 27141060 (PubMed) · PMC4900947 (PubMed Central)
  7. Immune activation caused by vascular oxidation promotes fibrosis and hypertension. Wu J, Saleh MA, Kirabo A, Itani HA, Montaniel KR, Xiao L, Chen W, Mernaugh RL, Cai H, Bernstein KE, Goronzy JJ, Weyand CM, Curci JA, Barbaro NR, Moreno H, Davies SS, Roberts LJ, Madhur MS, Harrison DG (2016) J Clin Invest 126(4): 1607
    › Primary publication · 27035819 (PubMed) · PMC4811163 (PubMed Central)
  8. CD70 Exacerbates Blood Pressure Elevation and Renal Damage in Response to Repeated Hypertensive Stimuli. Itani HA, Xiao L, Saleh MA, Wu J, Pilkinton MA, Dale BL, Barbaro NR, Foss JD, Kirabo A, Montaniel KR, Norlander AE, Chen W, Sato R, Navar LG, Mallal SA, Madhur MS, Bernstein KE, Harrison DG (2016) Circ Res 118(8): 1233-43
    › Primary publication · 26988069 (PubMed) · PMC4833561 (PubMed Central)
  9. Novel methods for microCT-based analyses of vasculature in the renal cortex reveal a loss of perfusable arterioles and glomeruli in eNOS-/- mice. Perrien DS, Saleh MA, Takahashi K, Madhur MS, Harrison DG, Harris RC, Takahashi T (2016) BMC Nephrol : 24
    › Primary publication · 26936597 (PubMed) · PMC4776352 (PubMed Central)
  10. Linking inflammation and hypertension via LNK/SH2B3. Dale BL, Madhur MS (2016) Curr Opin Nephrol Hypertens 25(2): 87-93
    › Primary publication · 26717315 (PubMed) · PMC4763980 (PubMed Central)

Community Leaders

Contact Information

2215 Garland Avenue
P415D Medical Research Building IV
Nashville, TN 37232
USA
615-875-3273 (p)

Meena Madhur
615-875-3273 (p)
Email

Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

Acute Kidney Injury Adoptive Transfer Adult Animals Benzylamines Cardiovascular Diseases Career Mobility CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Cohort Studies cytokine receptor Dietary Fats Drug Evaluation, Preclinical Genotype Hypertension Inflammation Interleukin 17 Kidney Glomerulus lymphocytes Neurotransmitter Agents Oxidative Stress Physicians Renal Dysfunction Sodium-Hydrogen Antiporter Superoxides Vascular Dysfunction Young Adult