Abstract
Bisphosphonates, the drugs used for the treatment of e.g. osteoporosis, inhibit the development of experimental atherosclerosis. When encapsulated in liposomes, they also inactivate macrophages, which have a key role in atherogenesis. We studied the effects of three clinically used bisphosphonates, i.e. clodronate, etidronate and pamidronate, on 1) the viability of mouse peritoneal macrophages and macrophage-like RAW 264 cells, 2) the degradation of 125I-labeled acetylated LDL by RAW 264 cells, and 3) the formation of LDL-derived foam cells in vitro. Liposome-encapsulated clodronate and pamidronate, but not etidronate, decreased the fraction of viable peritoneal macrophages in a concentration-dependent manner, whereas RAW 264 cells were much more resistant to the cytotoxic effects of bisphosphonates. Preincubation with liposomal clodronate and etidronate inhibited in a concentration-dependent manner the degradation of acetylated LDL in RAW 264 cells, but non-cytotoxic concentrations of liposomal pamidronate had only a weak inhibitory effect. The inhibition was more pronounced by liposomal clodronate than by liposomal etidronate. At high concentrations (500 microg protein/ml) of acetylated and aggregated LDL, RAW 264 cells trans...Continue Reading
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