Low density lipoprotein (LDL) receptor activity, measured as 125I‐LDL association and degradation at 37 °C, was determined in cultured fibroblasts from involved as well as uninvolved skin obtained from 20 psoriasis patients. The same analyses were conducted in fibroblasts from two reference groups consisting of 19 heterozygotes for familial hypercholesterolemia and 16 normal subjects, respectively.
Psoriasis patients had significantly lower LDL receptor activity than normals, and it was comparable to that of the heterozygotes for familial hypercholesterolemia. The reduced LDL receptor activity was not accompanied by an increase in total serum cholesterol. The psoriasis patients had a significant reduction in apo‐B concentration, but did not differ from the normals in the other serum lipid or lipoprotein parameters. There was no difference in LDL receptor activity between involved and uninvolved skin from psoriasis patients.
These results suggest that there is an abnormal cell membrane in dermal fibroblasts from psoriasis patients. Since their total serum cholesterol is normal, their low LDL receptor activity may be confined to dermal cells, leaving the hepatic lipid metabolism normal. The pathogenetic significance of this finding is unknown.
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 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 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. The difference was not statistically significant (P%0.11). However, fibroblast degradation of 125I‐LDL was significantly lower in cells from IHDs than in cells 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.
Lp(a) lipoprotein shares the apoB antigen with low density lipoprotein (LDL). The Lp(a) antigen is unique for Lp(a) lipoprotein. Fibroblast association (i.e. plasma membrane binding plus intracellular accumulation), plasma membrane binding, intracellular accumulation and degradation of 125I‐Lp(a) lipoprotein were studied in strains from subjects with or without autosomal dominant hypercholesterolemia (HC). Subjects without HC (non‐HCs) have cell surface receptors for low density lipoprotein (LDL receptors). On the average, HC heterozygotes have half‐normal LDL receptor activity and “receptor‐negative” HC homozygous cell strains lack functional receptors.
Fibroblast processing of 125I‐Lp(a) lipoprotein was compared to fibroblast processing of 125I‐LDL. LDL receptor‐dependent processing of 125I‐LDL was saturated at about 50 μg apo 125I‐LDL ml‐1 in non‐HC fibroblasts. 125I‐Lp(a) lipoprotein was, however, largely processed independently of receptor mechanisms by non‐HC cells (highest concentration examined 150 μg apo 125I‐Lp(a) lipoprotein ml‐1). Lp(a) lipoprotein did not interfere with 125I‐LDL for fibroblast association, but inhibited 125I‐LDL degradation. The interference with 125I‐LDL degradation was time dependent Only slightly higher 1251‐Lp(a) lipoprotein processing values were found in non‐HC and HC heterozygous strains than in “receptor‐negative” HC homozygous strains. However, non‐HC cells had more than tenfold higher 125I‐LDL processing values than “receptor‐negative” HC homozygous cells.
Serum reserve cholesterol binding capacity (SRCBC) was studied in 28 members of five kindreds with familial hypercholesterolemia (HC). A significantly lower SRCBC was found in family members heterozygous or homozygous for HC than in their healthy relatives. Hypothetically, the low SRCBC in HC patients could contribute to their propensity to develop premature atherosclerosis.
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