Machnik, Agnes and Neuhofer, Wolfgang and Jantsch, Jonathan and Dahlmann, Anke and Tammela, Tuomas and Machura, Katharina and Park, Joon-Keun and Beck, Franz-Xaver and Mueller, Dominik N. and Derer, Wolfgang and Goss, Jennifer and Ziomber, Agata and Dietsch, Peter and Wagner, Hubertus and van Rooijen, Nico and Kurtz, Armin and Hilgers, Karl F. and Alitalo, Kari and Eckardt, Kai-Uwe and Luft, Friedrich C. and Kerjaschki, Dontscho and Titze, Jens (2009) Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. NATURE MEDICINE, 15 (5). pp. 545-552. ISSN 1078-8956,
Full text not available from this repository. (Request a copy)Abstract
In salt-sensitive hypertension, the accumulation of Na(+) in tissue has been presumed to be accompanied by a commensurate retention of water to maintain the isotonicity of body fluids. We show here that a high-salt diet (HSD) in rats leads to interstitial hypertonic Na(+) accumulation in skin, resulting in increased density and hyperplasia of the lymphcapillary network. The mechanisms underlying these effects on lymphatics involve activation of tonicity-responsive enhancer binding protein (TonEBP) in mononuclear phagocyte system (MPS) cells infiltrating the interstitium of the skin. TonEBP binds the promoter of the gene encoding vascular endothelial growth factor-C (VEGF-C, encoded by Vegfc) and causes VEGF-C secretion by macrophages. MPS cell depletion or VEGF-C trapping by soluble VEGF receptor-3 blocks VEGF-C signaling, augments interstitial hypertonic volume retention, decreases endothelial nitric oxide synthase expression and elevates blood pressure in response to HSD. Our data show that TonEBP-VEGF-C signaling in MPS cells is a major determinant of extracellular volume and blood pressure homeostasis and identify VEGFC as an osmosensitive, hypertonicity-driven gene intimately involved in salt-induced hypertension.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NITRIC-OXIDE SYNTHASE; OSMOTICALLY INACTIVE NA+; TUMOR LYMPHANGIOGENESIS; INTERSTITIAL FLOW; SODIUM-BALANCE; DOCA-SALT; VEGF-C; RATS; HYPERTENSION; MICE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Sep 2020 07:36 |
| Last Modified: | 17 Sep 2020 07:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29084 |
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