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• W2884609926 abstract "A phenocopy is an environmentally-defined phenotype that mimics another, genetically-determined phenotype. The severity of hypercholesterolaemia, extent of down regulation of LDL receptor expression and aortic root localisation of atherosclerosis in cholesterol-fed rabbits strikingly resemble the cardinal features of homozygous familial hypercholesterolaemia (FH) in humans, suggesting that the former is a phenocopy of the latter. This review compares the metabolic and pathological consequences of induced hypercholesterolaemia in rabbits with those of homozygous FH and contrasts their ease of reversibility on resumption of a normal diet with the refractoriness to lipid-lowering therapy of homozygotes, in whom major adverse cardiovascular events and survival depend upon the prevailing level of serum cholesterol. The monofactorial nature of the atherosclerosis in both situations corroborates Anitschkow's concept that “Cholesterin ist alles.” In contrast, atherosclerosis in heterozygous FH differs in several respects from that of homozygotes, notably the lack of aortic root involvement and in its multifactorial aetiology, with raised LDL cholesterol, male gender, low HDL cholesterol and raised lipoprotein (a) all contributing to its clinical expression. In angiographic trials of LDL-lowering therapy regression of coronary lesions was observed in FH heterozygotes whereas they progressed in non-FH subjects. Similarly, carotid artery plaques progressed less in FH heterozygotes than in non-FH subjects, in both instances despite FH patients having higher LDL cholesterol levels on treatment. These findings suggest that, compared with non-FH subjects, atherosclerotic lesions in FH heterozygotes may be hyper-responsive to LDL-lowering therapy, whereas treatment of homozygous FH remains a major challenge." @default.
• W2884609926 created "2018-08-03" @default.
• W2884609926 creator A5039396185 @default.
• W2884609926 date "2018-09-01" @default.
• W2884609926 modified "2023-09-26" @default.
• W2884609926 title "Atherosclerosis in cholesterol-fed rabbits and in homozygous and heterozygous LDL receptor-deficient humans" @default.
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• W2884609926 doi "https://doi.org/10.1016/j.atherosclerosis.2018.07.032" @default.
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• W2884609926 hasPublicationYear "2018" @default.
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