Abstract
BackgroundProbucol is a unique hypolipidemic agent that decreases high density lipoprotein cholesterol (HDL-C). However, it is not definite that whether probucol hinders the progression of atherosclerosis by improving HDL function.MethodsEighteen New Zealand White rabbits were randomly divided into the control, atherosclerosis and probucol groups. Control group were fed a regular diet; the atherosclerosis group received a high fat diet, and the probucol group received the high fat diet plus probucol. Hepatocytes and peritoneal macrophages were isolated for [3H] labeled cholesterol efflux rates and expression of ABCA1 and SR-B1 at gene and protein levels; venous blood was collected for serum paraoxonase 1, myeloperoxidase activity and lipid analysis. Aorta were prepared for morphologic and immunohistochemical analysis after 12 weeks.ResultsCompared to the atherosclerosis group, the paraoxonase 1 activity, cholesterol efflux rates, expression of ABCA1 and SR-BI in hepatocytes and peritoneal macrophages, and the level of ABCA1 and SR-BI in aortic lesions were remarkably improved in the probucol group, But the serum HDL cholesterol concentration, myeloperoxidase activity, the IMT and the percentage plaque area of aorta were significantly decreased.ConclusionProbucol alleviated atherosclerosis by improving HDL function. The mechanisms include accelerating the process of reverse cholesterol transport, improving the anti-inflammatory and anti-oxidant functions.
Highlights
Probucol is a unique hypolipidemic agent that decreases high density lipoprotein cholesterol (HDLC)
At the end of the research, the results of the serum lipid suggested that hypercholesterolemia model was successfully established, serum triglyceride (TG), total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in atherosclerosis group were significantly higher than control group
Serum lipids were increased in probucol group as compared with control group, but TC, LDL-C and HDL-C in probucol group were significantly lower than atherosclerosis group
Summary
Probucol is a unique hypolipidemic agent that decreases high density lipoprotein cholesterol (HDLC). It is not definite that whether probucol hinders the progression of atherosclerosis by improving HDL function. Numerous epidemiological studies reported an inverse relationship between high density lipoprotein cholesterol (HDL-C) and the incidence of cardiovascular disease. The Milano people who carry the apolipoprotein A-I Milano mutant have low serum HDL-C levels but do not Probucol is a unique cholesterol lowering drug with anti-oxidant and anti-inflammatory properties that decreases HDL-C levels [6]. Probucol observational study illuminating therapeutic impact on vascular events (POSITIVE) showed that probucol was useful in lowering the risk of cardiovascular events in secondary prevention in spite of causing a decrease in HDL-C levels [8]. Probucol decreases HDL-C levels, it shows greatly controlled progression of atherosclerosis.
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