A Salt Sensing Kinase in T Lymphocytes, SGK1, Drives Hypertension and Hypertensive End-Organ Damage
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1 A Salt Sensing Kinase in T Lymphocytes, SGK1, Drives Hypertension and Hypertensive End-Organ Damage Allison E. Norlander 1, Mohamed A. Saleh 2,3, Arvind K. Pandey 4, Hana A. Itani 2, Jing Wu 1, Liang Xiao 2, Jay Kang 1, Bethany L. Dale 1, Slavina B. Goleva 1, Fanny Laroumanie 2, Liping Du 5, David G. Harrison 1,2, Meena S. Madhur* 1,2 1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA. 2 Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. 3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. 4 Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. 5 Vanderbilt Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Current address: Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
2 SUPPLEMENTAL MATERIAL Supplemental Figure 1. Cre recombinase expression in T cells does not affect Ang IIinduced blood pressure response. Telemetry recordings of (A) systolic blood pressures, (B) mean arterial pressures, (C) diastolic blood pressures, and (D) heart rates in tg CD4cre mice infused with Ang II (490ng/kg/min) for 28 days. Data were recorded for 2 days at baseline and weekly thereafter during Ang II infusion. All data are expressed as mean ± SEM (n = 5).
3 Supplemental Figure 2. T cell SGK1 deficiency prevents the chronic phase of Ang IIinduced vascular inflammation. (A) Representative flow cytometry dot plots showing gating strategy for T cell subsets (CD4 +, CD8 +, and CD3 + CD4 - CD8 - double negative (DN) cells) in single cell suspensions from the thoracic aorta of SGK1 fl/fl and SGK1 fl/fl tg CD4cre mice infused with Ang II or vehicle (Sham) for 7 or 28 days. (B-D) Summary data of absolute numbers of indicated cell types per thoracic aorta (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001; twoway ANOVA/Holm-Sidak s post hoc test; n = 7-12 per group). All data are expressed as mean ± SEM.
4 Supplemental Figure 3. T cell SGK1 deficiency prevents the chronic phase of Ang IIinduced renal inflammation. (A) Representative flow cytometry dot plots showing gating strategy for T cell subsets (CD4 +, CD8 +, and CD3 + CD4 - CD8 - double negative (DN) cells) in single cell suspensions from one kidney of SGK1 fl/fl and SGK1 fl/fl tg CD4cre mice infused with Ang II or vehicle (Sham) for 7 or 28 days. (B-D) Summary data of absolute numbers of indicated cell types per kidney (*P<0.01, **P<0.01; two-way ANOVA/Holm-Sidak s post hoc test; n=6-10 per group). All data are expressed as mean ± SEM.
5 Supplemental Figure 4. Vascular function is not impaired after 1 week of Ang II infusion. SGK1 fl/fl controls and SGK1 fl/fl tg CD4cre mice were infused with Ang II or vehicle (Sham) for 7 days. Endothelium-dependent relaxation to increasing doses of acetylcholine (Ach) was measured in (A) SGK1 fl/fl mice and (B) SGK1 fl/fl tg CD4cre mice, and endothelium-independent relaxation to increasing doses of sodium nitroprusside (SNP) was measured in (C) SGK1 fl/fl mice and (D) SGK1 fl/fl tg CD4cre mice. Data were analyzed by linear regression; n=5-7 per group. All data are expressed as mean ± SEM.
6 Supplemental Figure 5. Frequency of splenic Th1/Tc1 cells is not altered by Ang II infusion or loss of T cell SGK1. (A) Representative flow cytometry dot plots for CD4 + IFNγ + Th1 cells and CD8 + IFNγ + Tc1 cells in splenic single cell suspensions from SGK1 fl/fl and SGK1 fl/fl tg CD4cre mice infused with Ang II or vehicle (Sham) for 28 days. (B-C) Summary data of percentages of CD4 + IFNγ + Th1 cells out of total CD4 + cells and CD8 + IFNγ + Tc1 cells out of total CD8 + cells in the indicated groups. All data are expressed as mean ± SEM (n=9-12 per group).
7 Supplemental Figure 6. SGK1 expression in splenic T cell subsets and peripheral blood T and non-t cell fractions in SGK1 fl/fl controls and SGK1 fl/fl tg CD4cre mice. Naïve CD4 + T cells (A), naive CD8 + T cells (B), or γδ T cells (C) were isolated from spleens of SGK1 fl/fl control and SGK1 fl/fl tg CD4cre mice and cultured for 3 days on anti-cd3/anti-cd28 coated plates in the presence of Th17 polarizing cytokines plus an excess 40mM NaCl to maximize SGK1 expression which was then quantified by qrt-pcr. SGK1 expression was also quantified by qrt-pcr from peripheral blood CD3 + T cells and all other PBMCs isolated from SGK1 fl/fl control and SGK1 fl/fl tg CD4cre mice. *P<0.05, **P<0.01, ****P<0.0001; Student s t-test; n = 4-10 per group. All data are expressed as mean ± SEM.
8 Supplemental Table 1. Sodium channels and transporters expressed by T cells. Pan CD3 + T cells were isolated from spleens of C57Bl/6J wild type mice. The indicated sodium channels/transporters were detected by RT-PCR.
A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage
A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage Allison E. Norlander, 1 Mohamed A. Saleh, 2,3 Arvind K. Pandey, 4 Hana A. Itani, 2 Jing Wu, 1 Liang Xiao,
Lymphocyte adaptor protein LNK deficiency exacerbates hypertension and end-organ inflammation
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M.Sc. in Pharmacology & Toxicology, 2004 Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
Mohamed A. Saleh, B.Pharm., Ph.D. Post-Doctoral Fellow, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA 37232 and Lecturer at the Department
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SUPPLEMENT Supplementary Figure 1: (A) (B)
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Supplemental Table I Male / Mean ± SEM n Mean ± SEM n Body weight, g 29.2±0.4 17 29.7±0.5 17 Total cholesterol, mg/dl 534.0±30.8 17 561.6±26.1 17 HDL-cholesterol, mg/dl 9.6±0.8 17 10.1±0.7 17 Triglycerides,
Supplementary. presence of the. (c) mrna expression. Error. in naive or
Figure 1. (a) Naive CD4 + T cells were activated in the presence of the indicated cytokines for 3 days. Enpp2 mrna expression was measured by qrt-pcrhr, infected with (b, c) Naive CD4 + T cells were activated
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Supplemental Figure 1 1a 1c PD-1 MFI fold change 6 5 4 3 2 1 IL-1α IL-2 IL-4 IL-6 IL-1 IL-12 IL-13 IL-15 IL-17 IL-18 IL-21 IL-23 IFN-α Mut Human PD-1 promoter SBE-D 5 -GTCTG- -1.2kb SBE-P -CAGAC- -1.kb
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Supplementary Figure 1
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Your Guide to High Blood Pressure
Your Guide to The Bon Secours Heart Team focuses on your complete cardiovascular care. It s our goal to help you be well. An important part of your heart health is maintaining a healthy blood pressure
Supplemental Information. CD4 + CD25 + Foxp3 + Regulatory T Cells Promote. Th17 Cells In Vitro and Enhance Host Resistance
Immunity, Volume 34 Supplemental Information D4 + D25 + + Regulatory T ells Promote Th17 ells In Vitro and Enhance Host Resistance in Mouse andida albicans Th17 ell Infection Model Pushpa Pandiyan, Heather
Nature Immunology doi: /ni.3268
Supplementary Figure 1 Loss of Mst1 and Mst2 increases susceptibility to bacterial sepsis. (a) H&E staining of colon and kidney sections from wild type and Mst1 -/- Mst2 fl/fl Vav-Cre mice. Scale bar,
Human Immunodeficiency Virus Type-1 Myeloid Derived Suppressor Cells Inhibit Cytomegalovirus Inflammation through Interleukin-27 and B7-H4
Human Immunodeficiency Virus Type-1 Myeloid Derived Suppressor Cells Inhibit Cytomegalovirus Inflammation through Interleukin-27 and B7-H4 Ankita Garg, Rodney Trout and Stephen A. Spector,,* Department
c Ischemia (30 min) Reperfusion (8 w) Supplementary Figure bp 300 bp Ischemia (30 min) Reperfusion (4 h) Dox 20 mg/kg i.p.
a Marker Ripk3 +/ 5 bp 3 bp b Ischemia (3 min) Reperfusion (4 h) d 2 mg/kg i.p. 1 w 5 w Sacrifice for IF size A subset for echocardiography and morphological analysis c Ischemia (3 min) Reperfusion (8
LPS CD40 + IL-4. Vorinostat (24 Hours) Vorinostat (24 Hours) Panobinostat (24 Hours) Panobinostat (24 Hours) Romidepsin (48 Hours)
A) CD + IL- B) LPS ( Hours) ( Hours) Cell number (x1-3 ) 1 1 3.7 M 1. M. M.1 M Cell number (x1 - ) 1 1 3. M 1. M.7 M.38 M Cell number (x1-3 ) Cell number (x1-3 ) 3 1 1 1 ( Hours) 7.nM.nM 1.7nM.nM Romidepsin
Nature Medicine: doi: /nm.3922
Title: Glucocorticoid-induced tumor necrosis factor receptor-related protein co-stimulation facilitates tumor regression by inducing IL-9-producing helper T cells Authors: Il-Kyu Kim, Byung-Seok Kim, Choong-Hyun
Supplementary Figure 1 (Mu) SBP (mmhg) 2 18 16 p Using the New Hypertension Guidelines
Using the New Hypertension Guidelines Kamal Henderson, MD Department of Cardiology, Preventive Medicine, University of North Carolina School of Medicine Kotchen TA. Historical trends and milestones in
Summary of recommendations
Summary of recommendations Measuring blood pressure (BP) Use the recommended technique at every BP reading to ensure accurate measurements and avoid common errs. Pay particular attention to the following:
Nature Immunology: doi: /ni Supplementary Figure 1. Gene expression profile of CD4 + T cells and CTL responses in Bcl6-deficient mice.
Supplementary Figure 1 Gene expression profile of CD4 + T cells and CTL responses in Bcl6-deficient mice. (a) Gene expression profile in the resting CD4 + T cells were analyzed by an Affymetrix microarray
E10.5 E18.5 P2 10w 83w NF1 HF1. Sham ISO. Bmi1. H3K9me3. Lung weight (g)
Myociyte cross-sectional Relative mrna levels Relative levels Relative mrna levels Supplementary Figures and Legends a 8 6 4 2 Ezh2 E1.5 E18.5 P2 1w 83w b Ezh2 p16 amhc b-actin P2 43w kd 37 86 16 wt mouse
Nature Immunology: doi: /ni Supplementary Figure 1. Characteristics of SEs in T reg and T conv cells.
Supplementary Figure 1 Characteristics of SEs in T reg and T conv cells. (a) Patterns of indicated transcription factor-binding at SEs and surrounding regions in T reg and T conv cells. Average normalized
Supplementary Figure S1: Alignment of CD28H. (a) Alignment of human CD28H with other known B7 receptors. (b) Alignment of CD28H orthologs.
Supplementary Figure S1: Alignment of CD28H. (a) Alignment of human CD28H with other known B7 receptors. (b) Alignment of CD28H orthologs. Predicted CD28H protein sequences from human, chimpanzee (pan
Update on Airborne Pollution and Blood Pressure
Update on Airborne Pollution and Blood Pressure Philippe van de Borne Hôpital Erasme Department of cardiology Brussels - Belgium 10h30-11h00 Friday 4 th March 2016 http://urgencesgrece.eu/fr http://urgencesgrece.eu/fr
Supplementary Figure 1: Hsp60 / IEC mice are embryonically lethal (A) Light microscopic pictures show mouse embryos at developmental stage E12.
Supplementary Figure 1: Hsp60 / IEC mice are embryonically lethal (A) Light microscopic pictures show mouse embryos at developmental stage E12.5 and E13.5 prepared from uteri of dams and subsequently genotyped.