Bisphosphonates induce inflammation and rupture of atherosclerotic plaques in apolipoprotein-E null mice

Mona Shimshi, Etsuko Abe, Edward A. Fisher, Mone Zaidi, John T. Fallon

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


The apolipoprotein E knockout (Apo-E-/-) mouse is a well-known model of atherosclerosis. Bisphosphonates, through their affinity to hydroxyapatite, are known to reduce arterial calcification in several animal models. Thus, we examined the effect of two therapeutically used oral bisphosphonates, alendronate and risedronate, on plaque formation in the Apo-E-/- mouse. The drugs were administered by gavage to 16-week-old Apo-E-/- mice for 8 weeks. At 8 weeks, there was no difference in bone mineral density (BMD) of the alendronate- and risedronate-treated mice at any site. A time-dependent increase in BMD was demonstrated in Apo-E -/- mice with risedronate (p < 0.01). Histological evaluation revealed that both bisphosphonates caused atherosclerotic plaque rupture. Five of 17 mice had severe inflammation with or without plaque rupture, while seven mice showed inflammation, but without plaque rupture. Neither caspase 3 nor metalloproteinases 2 and 9 were increased in ruptured plaques on immunocytochemistry. Quantitative measurements of arterial caliber remained unaffected. Our finding of plaque inflammation and rupture in bisphosphonate-treated Apo-E-/- mice may provide the first animal model for studies aimed at characterizing mechanisms of plaque rupture in animal models.

Original languageEnglish
Pages (from-to)790-793
Number of pages4
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - 18 Mar 2005


  • Atherosclerosis
  • Drugs
  • Inflammation
  • Plaques
  • Thrombosis


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