A neutralizing antibody against receptor for advanced glycation end products (RAGE) reduces atherosclerosis in uremic mice

Susanne Bro, Allan Flyvbjerg, Christoph J. Binder, Christian A. Bang, Larry Denner, Klaus Olgaard, Lars B. Nielsen

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Chronic renal failure markedly accelerates atherogenesis in apolipoprotein E-deficient (apoE-/-) mice. To study the putative role of receptor for advanced glycation end products (RAGE) in development of uremic atherosclerosis, apoE-/- mice received intraperitoneal injections thrice weekly of a neutralizing murine RAGE-antibody (RAGE-ab) (n = 21) or an isotype-matched control antibody (placebo-ab) (n = 23). Treatment was started 4 weeks after surgical 5/6 nephrectomy in 16 weeks old mice and continued for 12 weeks. The RAGE-ab did not affect blood pressure, plasma cholesterol or measures of uremia. However, the aortic plaque area fraction was reduced by 59% in RAGE-ab compared with placebo-ab-treated mice (0.016 ± 0.002 versus 0.039 ± 0.005, P < 0.001). In plasma, the RAGE-ab reduced concentrations of oxidized phospholipid neo-epitopes in plasma as detected by the specific monoclonal antibody EO6 (P < 0.05) and titers of IgG antibodies against oxidized low-density lipoprotein (P < 0.001). In the aorta of treated mice, the RAGE-ab did not affect the mRNA expression of eight selected genes associated with inflammation. The results suggest that blockade of RAGE reduces the proatherogenic effects of uremia, possibly through a systemic decrease in oxidative stress.

Original languageEnglish (US)
Pages (from-to)274-280
Number of pages7
JournalAtherosclerosis
Volume201
Issue number2
DOIs
StatePublished - Dec 1 2008

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Keywords

  • Antibodies against oxidized low density lipoprotein
  • Atherosclerosis
  • EO6
  • ICAM-1
  • Oxidized phospholipid neo-epitopes
  • Receptor for advanced glycation end products
  • Renal failure
  • VCAM-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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