Comment on 'The great cholesterol myth: unfortunate consequences of Brown and Goldstein's mistake'

Abstract

ARTICLE Sir, Adams1 proposes that the accelerated arterial disease of familial hypercholesterolaemia (FH) is the consequence of more ‘brittle’ cell walls which result from an inability to take up cholesterol via the low density lipoprotein (LDL) receptor leading to a loss of membrane fluidity and an inability to withstand normal haemodynamic stresses. This he asserts is the basis of the premature atherosclerosis; not the greatly increased concentrations of circulating LDL—a mechanism that he describes as ‘Brown and Goldstein's mistake’. Adams notes that FH cells in culture, unlike those from normal individuals, do not suppress endogenous cholesterol synthesis in the presence of increasing concentrations of LDL in the medium. He fails to consider the possibility that this endogenous alternative source of cellular cholesterol may prevent a significant depletion of membrane cholesterol. Moreover, in FH the plasma membranes of cells will be exposed to higher than normal …