Aim: Cholesterol supplemented diet, in rabbit, triggers severe hypercholesterolemia which rapidly (less than 2 months) evolves to atherosclerosis. This work aimed to ascertain whether plasma factors playing key roles in the reverse cholesterol transport, such as the activity of the enzyme LCAT and the level of the apolipoprotein (Apo) A-I, are altered during the atherosclerosis rising and progression. Methods: New Zealand rabbits were fed with normal (N=6) or 2% cholesterol enriched (N=6) diet. Serum was collected at 0, 4 and 8 weeks, and analysed for Apo A-I level (by ELISA) and LCAT activity in vitro (assaying free 3H-cholesterol conversion into ester form) or in vivo (measuring by HPLC the amounts of both free and ester forms from isolated HDL). Results: Apo A1 was found decreased in the treated animals (t=4w: 65.5±3.4 vs 95.7±3.6 µg/ml in controls, P<0.01; t=8w: 39±4.1 vs 97.3 ±5.4 µg/ml in controls, P<0.01). LCAT exhibited lower activity both in vitro (t=4w: 3.3±0.8 vs 7.8±0.6 U in controls, P<0.01; t=8w: 3.9±0.9 vs 8.1±0.7 U in controls, P<0.01) and in vivo (ratio of ester with free form of cholesterol at 4w: 3.6±0.5 vs 6.6±0.4 in controls, P<0.01; ratio at 8w: 3.4±0.6 vs 6.3±0.3 in controls, P<0.01). Conclusions: Apo A1, which is known to stimulate LCAT for cholesterol esterification, exhibits plasma level decreasing as atherosclerosis rises up. Accordingly, the LCAT function decreases during the treatment. Reduced levels of Apo A1 and LCAT significantly contribute to atherosclerosis as negatively affecting the efficiency of reverse cholesterol transport.

Atherogenesis in rabbit is associated with decreased LCAT activity and Apo A-I level.

CIGLIANO, LUISA;ABRESCIA, PAOLO
2006

Abstract

Aim: Cholesterol supplemented diet, in rabbit, triggers severe hypercholesterolemia which rapidly (less than 2 months) evolves to atherosclerosis. This work aimed to ascertain whether plasma factors playing key roles in the reverse cholesterol transport, such as the activity of the enzyme LCAT and the level of the apolipoprotein (Apo) A-I, are altered during the atherosclerosis rising and progression. Methods: New Zealand rabbits were fed with normal (N=6) or 2% cholesterol enriched (N=6) diet. Serum was collected at 0, 4 and 8 weeks, and analysed for Apo A-I level (by ELISA) and LCAT activity in vitro (assaying free 3H-cholesterol conversion into ester form) or in vivo (measuring by HPLC the amounts of both free and ester forms from isolated HDL). Results: Apo A1 was found decreased in the treated animals (t=4w: 65.5±3.4 vs 95.7±3.6 µg/ml in controls, P<0.01; t=8w: 39±4.1 vs 97.3 ±5.4 µg/ml in controls, P<0.01). LCAT exhibited lower activity both in vitro (t=4w: 3.3±0.8 vs 7.8±0.6 U in controls, P<0.01; t=8w: 3.9±0.9 vs 8.1±0.7 U in controls, P<0.01) and in vivo (ratio of ester with free form of cholesterol at 4w: 3.6±0.5 vs 6.6±0.4 in controls, P<0.01; ratio at 8w: 3.4±0.6 vs 6.3±0.3 in controls, P<0.01). Conclusions: Apo A1, which is known to stimulate LCAT for cholesterol esterification, exhibits plasma level decreasing as atherosclerosis rises up. Accordingly, the LCAT function decreases during the treatment. Reduced levels of Apo A1 and LCAT significantly contribute to atherosclerosis as negatively affecting the efficiency of reverse cholesterol transport.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/368115
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