Low density lipoprotein receptor activity in cultured fibroblasts from subjects with or without ischemic heart disease (in the absence of familial hypercholesterolemia)*

Abstract

Fibroblast strains from 6 subjects with ischemic heart disease (IHD) were compared to strains from 43 subjects without a history of IHD (non-IHD), with respect to association (plasma membrane binding plus intracellular accumulation) and degradation of radio-iodinated LDL (125I-LDL). The subjects (25 females and 24 males) were selected on the criteria that they were twins (one from each pair), 58-61 yr old, and living within 200 km of Oslo. None of them suffered from autosomal, dominant hypercholesterolemia, which is associated with reduced cell surface LDL receptor activity and increased susceptibility to IHD. There was a trend towards lower 125I-LDL association values in strains from IHD than in strains from non-IHD. The difference was not statistically significant (P = 0.11). Fibroblast degradation of 125I-LDL was significantly lower in cells from IHD than in cells from non-IHD (P = 0.009). There was a significant negative correlation between, on one hand, serum total cholesterol level and on the other fibroblast association (P = 0.03) or degradation (P = 0.04) of 125I-LDL. Fibroblast association of LDL may be determined by alternate genes at one single locus. Together with the present limited data, this raises the possibility that normal genes at the LDL receptor locus may render subjects more or less susceptible to ischemic heart disease.