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

Fibroblast strains from six subjects with ischemic heart disease (IHDs) were compared to strains from 43 subjects without a history of IHD (non-IHDs), with respect to association (plasma membrane binding plus intracellular accumulation) and degradation of radioiodinated 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 years 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 IHDs than in strains from non-IHDs (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. We have previously presented data indicating that 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.