Renal inflammation and injury are associated with lymphangiogenesis in hypertension

Sterling C. Kneedler, Lauren E. Phillips, Kayla R. Hudson, Katharine M. Beckman, Catalina A. Lopez Gelston, Joseph M. Rutkowski, Alan R. Parrish, Peter A. Doris, Brett M. Mitchell

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Lymphatic vessels are vital for the trafficking of immune cells from the interstitium to draining lymph nodes during inflammation. Hypertension is associated with renal infiltration of activated immune cells and inflammation; however, it is unknown how renal lymphatic vessels change in hypertension. We hypothesized that renal macrophage infiltration and inflammation would cause increased lymphatic vessel density in hypertensive rats. Spontaneously hypertensive rats (SHR) that exhibit hypertension and renal injury (SHR-A3 strain) had significantly increased renal lymphatic vessel density and macrophages at 40 wk of age compared with Wistar-Kyoto (WKY) controls. SHR rats that exhibit hypertension but minimal renal injury (SHR-B2 strain) had significantly less renal lymphatic vessel density compared with WKY rats. The signals for lymphangiogenesis, VEGF-C and its receptor VEGF-R3, and proinflammatory cytokine genes increased significantly in the kidneys of SHR-A3 rats but not in SHR-B2 rats. Fischer 344 rats exhibit normal blood pressure but develop renal injury as they age. Kidneys from 24-mo- and/or 20-mo-old Fischer rats had significantly increased lymphatic vessel density, macrophage infiltration, VEGF-C and VEGF-R3 expression, and proinflammatory cytokine gene expression compared with 4-mo-old controls. These data together demonstrate that renal immune cell infiltration and inflammation cause lymphangiogenesis in hypertension- and aging-associated renal injury.

Original languageEnglish (US)
Pages (from-to)F861-F869
JournalAmerican Journal of Physiology - Renal Physiology
Volume312
Issue number5
DOIs
StatePublished - May 2017

Keywords

  • Hypertension
  • Inflammation
  • Kidney
  • Lymphatic endothelial cells
  • Lymphatics

ASJC Scopus subject areas

  • Physiology
  • Urology

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    Kneedler, S. C., Phillips, L. E., Hudson, K. R., Beckman, K. M., Lopez Gelston, C. A., Rutkowski, J. M., Parrish, A. R., Doris, P. A., & Mitchell, B. M. (2017). Renal inflammation and injury are associated with lymphangiogenesis in hypertension. American Journal of Physiology - Renal Physiology, 312(5), F861-F869. https://doi.org/10.1152/ajprenal.00679.2016