Inverse correlation between vascular endothelial growth factor back-filtration and capillary filtration pressures

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Abstract
Vascular endothelial growth factor A (VEGF) is an essential growth factor during glomerular development and postnatal homeostasis. VEGF is secreted in high amounts by podocytes into the primary urine, back-filtered across the glomerular capillary wall to act on endothelial cells. So far it has been assumed that VEGF back-filtration is driven at a constant rate exclusively by diffusion. In the present work, glomerular VEGF back-filtration was investigated in vivo using a novel extended model based on endothelial fenestrations as surrogate marker for local VEGF concentrations. Single nephron glomerular filtration rate (SNGFR) and/or local filtration flux were manipulated by partial renal mass ablation, tubular ablation, and in transgenic mouse models of systemic or podocytic VEGF overexpression or reduction. Our study shows positive correlations between VEGF back-filtration and SNGFR as well as effective filtration rate under physiological conditions along individual glomerular capillaries in rodents and humans. Our results suggest that an additional force drives VEGF back-filtration, potentially regulated by SNGFR.
Funding Information
  • Deutsche Forschungsgemeinschaft
  • DFG (DFG MO 1082/7-1)
  • STOP-FSGS
  • German Ministry for Science and Education
  • BMBF (01GM1518A)
  • Excellence Initiative by the German Federal and State Governments
  • START
  • Faculty of Medicine of the RWTH Aachen University
  • Else-Kröner-Fresenius Foundation (A200/2013, 2015/A197)
  • Interdisciplinary Center for Clinical Research
  • Faculty of Medicine of RWTH Aachen University
  • NIH (RO1-DK59333, P30-DK-07910)

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