Na-MRI can help us find the salt

Transcription

1 Na-MRI can help us find the salt Signal 1,5 1 0,5 0 TE = 2 3 ms w Na = g Na B -0, t in ms Signal Einhüllende

2 Sodium research quo vadis? Hypertension, 2012 Hypertension, 2013 Kidney International 2015

3 storage and cardiovascular outcome J Am Soc Nephrol. 2017

4 Age storage Why would we kill ourselves? ENCEPHALOMYELITIS HYPERTENSION CVD

5 Salt barrier formation to ward off infections Cell Metabolism, 2015

6 Salt barrier formation to ward off infections Cell Metabolism, 2015

7 Salt barrier formation to ward off infections Cell Metabolism, 2015

8 INFLAMMATORY RESPONSE Host- Defense Age Salt Intake MPS cells NFAT5/NOS2 + storage Barrier Function AUTOIMMUNITY HYPERTENSION CVD Immune Cell Action

9 Autoimmunity a mislead host defense. Nature, 2013

10 INFLAMMATORY RESPONSE Host- Defense Age Salt Intake T cells NFAT5/IL-17 MPS cells NFAT5/NOS2 + storage Barrier Function AUTOIMMUNITY HYPERTENSION CVD Immune Cell Action

11 Local control of salt metabolism by homeostatic immune cells

12 Kidney Clearance Blood Skin Equilibrium What I have learned at school Urine Cl -

13 Skin sodium storage in guinea pigs and rats Stratum Corneum Stratum Granulosum Stratum Spinosum 30 mmol/kg 160 mmol/kg 374 mmol/kg Stratum Germinativum Dermis 313 mmol/kg 530 mmol/kg Keratinocyte Blood vessel J Investig Dermatol 79(3): , 1982 Lymph vessel Pflugers Arch - Eur J Physiol 467: , 2015

14 Skin sodium storage and hypertension in rats Keratinocyte Blood vessel Lymph vessel Nikpey et al, Hypertension, 2017

15 7T Na-MRI can help us find the salt much better NMR in Biomed 28: 54 62, 2015

16 Kidney Clearance Blood Skin Equilibrium The problem with what I have learned at school Urine Cl -

17 Tauber AI. Nat Rev Mol Cell Biol Nov;4(11): What is immune function? Physiological inflammation: Phagocytes are engaged in essentially the same process clearing the body of dysfunctional elements (endogenous other ) and unwanted external intruders.

18 Kidney Clearance 2 Blood S-S Clearance 1 Skin Interstitium NFAT 5 Cl - Na+ _ Lymph Vessel Cl - VEGF-C VEGFR-3 Lymph Vessel Nature Medicine, 2009 Hypertension, 2010 Urine Cl -

19 S-S enos enos enos LSD HSD Blood: [ + K + ] 143 ± 2 mm 145 ± 2 mm Skin: [ + K + ] 177 ± 8*mM 191 ± 7 * mm LSD Anti-VEGF-C LSD HSD HSD Anti-ß Actin 50 µm 50 µm NO _ Cl - NFAT 5 _ NO NO VEGFR-2 VEGF-C VEGFR-3 Blood Vessel Interstitium Lymph Hyperplastic VesselLymph Vessel Nature Med, 2009 Hypertension, 2010

20 J Clin Invest, 2013 Macrophages VEGF-C and vermittelte skin Regulation electrolytes der - und and Volumenhomöostase pressure A C 0.08 Skin chloride 0.08 mmol g DW mmol ml -1 B 0.00 n = 2 n = 3 n = 2 n = 3 SKCl - SKCl - / SKW 0.00 D FVB HSD LSD LysM wt/wt TonEBP flox/flox LysM wt/cre TonEBP flox/flox 500 µm 500 µm 500 µm

21 INFLAMMATORY RESPONSE Host- Defense Age Salt Intake T cells NFAT5/IL-17 MPS cells NFAT5/NOS2 + AUTOIMMUNITY HYPERTENSION CVD storage Barrier Function Immune Cell Action - HOMEOSTATIC RESPONSE MPS cells NFAT5/VEGF-C CLEARANCE BP BUFFERING CVD PREVENTION

22 B cells in salty microenvironments www-s.acm.illinois.edu

23 B cells in salty microenvironments Lilijana Rokvic Wolfgang Schuh Hans-Martin Jäck work in progress

24 INFLAMMATORY RESPONSE Host- Defense Age Salt Intake T cells NFAT5/IL-17 MPS cells NFAT5/NOS2 B cells NFAT5/? AUTOIMMUNITY HYPERTENSION CVD + - storage Barrier Function Immune Cell Action HOMEOSTATIC RESPONSE MPS cells NFAT5/VEGF-C CLEARANCE BP BUFFERING CVD PREVENTION

25 Salty microenvironments: a need to bring material sciences into medicine Embedding Stojan Perisic Joachim Spatz 1. Planing 2. Freeze-drying 3. SEM+EDX Rosendaal et al 2009, modified work in progress

26 work in progress Salty microenvironments: a need to bring material sciences into medicine µm

27 B cells in salty microenvironments mb1 cre Nfat5 flox mice: * Skin Lymph Node work in progress

28 work in progress B cells in salty microenvironments mb1 cre Nfat5 flox mice: salt-sensitive hypertension

29 INFLAMMATORY RESPONSE Host- Defense Age Salt Intake Race Gender T cells NFAT5/IL-17 MPS cells NFAT5/NOS2 B cells NFAT5/? AUTOIMMUNITY HYPERTENSION CVD + - storage Barrier Function Immune Cell Action HOMEOSTATIC RESPONSE MPS cells NFAT5/VEGF-C B cells NFAT5/? CLEARANCE BP BUFFERING CVD PREVENTION

30 State of the art and an alternative Kidney International, 2014

31 State of the art and an alternative Kidney International, 2015