Low‐density‐lipoprotein‐receptor mRNA content of fibroblasts from normal and familial hypercholesterolaemic subjects

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Abstract
The amount of mRNA for the low-density-lipoprotein (LDL) receptor in cultured human fibroblasts was estimated by hybridization of the poly(A)-rich RNA fraction with a DNA probe, using the recovery of .beta.-actin mRNA to correct for losses. During incubation of the cells with lipoprotein-deficient serum (LPDS) both LDL-receptor mRNA content and the rate of receptor protein synthesis increaed fourfold during the first 16 h and then fell by approximately 50% durign the next 24 h. The content of .beta.-actin mRNA fell by a similar amount, so that the ratio of receptor/.beta.-actin mRNAs rose and then remained constant. The fall in .beta.-actin mRNA content during incubation with LPDS was not prevented by the addition of cholesterol to the medium. In cells from a homozygous familial hypercholesterolaemic (FH) subject that bound 20% of the normal amount of LDL, the content of LDL-receptor mRNA an the changes during incubation with LPDS or free sterols were similar to normal. Cells from a familial hypercholesterolaemic subject that produced no immunodetectable receptor protein produced a small amount of receptor mRNA of apparently normal size which responded in the same way as in normal cells to LPDS and free sterols.