CHOLESTEROL MOBILIZATION AND REGRESSION OF ATHEROMA IN CHOLESTEROL-FED RABBITS INDUCED BY LARGE UNILAMELLAR VESICLES

The antiatherogenic properties of repeated injections of egg phosphati dylcholine large unilamellar vesicles (LUVs) of 100 nm diameter were t ested in an experimental model for atherosclerosis. Forty eight rabbit s were divided into two diet groups fed standard rabbit chow or fed a cholesterol-enriched diet (0.5% by weight) to induct the formation of atherosclerotic lesions. Prior to the initiation of LUV therapy, the c holesterol diet was ceased and all animals were returned to standard r abbit chow, The treatment protocol consisted of a total of 10 bolus in jections of vesicles, at a phospholipid dose of 300 mg/kg body weight or the equivalent volume of saline, with one injection given to each a nimal every 10 days, LUV injections brought about a large movement of cholesterol into the blood pool and resulted in a significant reductio n in the cholesterol content as well as the degree of surface plaque i nvolvement of aortic tissue in atherosclerotic animals. Most notably, the thoracic aorta of LUV-treated animals exhibited a 48% reduction in tissue cholesterol content per gram of protein compared to saline-tre ated controls. Histochemical analyses revealed that aortas from animal s receiving the repeated injections of LUVs displayed less cholesterol deposits in lesions, and a moderate reduction in intimal-to-medial th ickness. This repression of atheroma, induced by LUV therapy, was obse rved even though animals possessed persistent elevated plasma choleste rol levels after the cholesterol-enriched diet was ceased. These resul ts suggest that repeated injections of LUVs, working with endogenous H DL, may be a useful therapy in the management of atherosclerosis. (C) 1998 Elsevier Science B.V.