Renal tubular epithelial cells mimic endothelial cells upon exposure to oxidized LDL

Anupam Agarwal, József Balla, György Balla, Anthony J. Croatt, Gregory M. Vercellotti, Karl A. Nath

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


In protein-uric states, renal tubular epithelial cells are exposed to diverse macromolecules, including low-density lipoproteins (LDL), normally excluded from the urinary space. Oxidized LDL (LDLOX) is incriminated in atherogenesis and glomerulosclerosis. Since urine is prooxidant, we considered whether LDLOX injures renal tubular epithelial cells (LLC-PK1). We demonstrate that the cytotoxicity of LDLOX on LLC-PK1 cells resembles its toxicity to human umbilical vein endothelial cells (HUVEC) in that oxidized but not native LDL is injurious. Pretreatment of LLC-PK1 cells and HUVEC with antioxidants markedly reduced the cytotoxicity of LDLOX. Pretreatment of LDL with antioxidants, prior to oxidation of LDL, vitiated its cytotoxicity. That LDLOX is prooxidant was supported by expression of heme oxygenase, a redox-sensitive enzyme. LDLOX induced heme oxygenase mRNA and enzyme activity. Pretreatment of LDL with antioxidants prior to oxidation attenuated heme oxygenase mRNA induction in LLC-PK1 and HUVEC. An iron chelator prevented cytotoxicity and heme oxygenase expression induced by LDLOX. Based on these effects of LDLOX, we draw an analogy between tubulointerstitial disease and atherogenesis and speculate that LDLOX contributes to tubulointerstitial disease in proteinuric states.

Original languageEnglish (US)
Pages (from-to)F814-F823
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number4 40-4
StatePublished - 1996


  • Atherosclerosis
  • Heme oxygenase
  • Iron
  • Proteinuria
  • Renal tubule

ASJC Scopus subject areas

  • Physiology


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