The skin interstitium sequesters excess Na+ and Cl– in salt-sensitive hypertension. Mononuclear phagocyte system (MPS) cells are recruited to the skin, sense the hypertonic electrolyte accumulation in skin, and activate the tonicity-responsive enhancer-binding protein (TONEBP, also known as NFAT5) to initiate expression and secretion of VEGFC, which enhances electrolyte clearance via cutaneous lymph vessels and increases eNOS expression in blood vessels. It is unclear whether this local MPS response to osmotic stress is important to systemic blood pressure control. Herein, we show that deletion of
Helge Wiig, Agnes Schröder, Wolfgang Neuhofer, Jonathan Jantsch, Christoph Kopp, Tine V. Karlsen, Michael Boschmann, Jennifer Goss, Maija Bry, Natalia Rakova, Anke Dahlmann, Sven Brenner, Olav Tenstad, Harri Nurmi, Eero Mervaala, Hubertus Wagner, Franz-Xaver Beck, Dominik N. Müller, Dontscho Kerjaschki, Friedrich C. Luft, David G. Harrison, Kari Alitalo, Jens Titze
A skin-specific VEGFC trap in mice with overexpression of sVEGFR3 in keratinocytes (K14-FLT4 mice) leads to cutaneous lymphatic capillary hypoplasia, skin electrolyte retention, and salt-sensitive blood pressure increase.