The interaction of Lp(a) with normal and LDL-receptor-deficient human skin fibroblasts.
The role of LDL receptors in the in vivo catabolism of Lp(a) is still a matter of controversy. Since Lp(a) binds LDL with high affinity, it was essential for this study to separate Lp(a) quantitatively from all other apo-B and apo-E-containing lipoproteins. This was achieved by the addition of proline as a dissociating agent to all buffers during Lp(a) preparation. Normal human skin fibroblasts pre-incubated with 40 mg/ml of Lp(a) downregulated cholesterol biosynthesis by approx. 35%; the same amount of LDL caused a 90% reduction. Cholesterol biosynthesis of LDL-receptor-deficient fibroblasts was not affected at all by LDL, yet Lp(a) exhibited a similar effect as in normal fibroblasts (32% reduction). An LDL-receptor-independent uptake of Lp(a) into fibroblasts must therefore be postulated. We also studied the degradation of Lp(a) in normal fibroblasts in comparison with LDL. Pure Lp(a) was only slightly degraded in relation to LDL. If fibroblasts were pre-incubated with small amounts of LDL, Lp(a) degradation was enhanced by a factor of 3-5. This effect was even more pronounced in fibroblasts pre-incubated with mevinolin. Thus the LDL receptor may play an indirect role in Lp(a) catabolism. The significance of these findings for the in vivo metabolism of Lp(a) remains to be established.
Kostner
G M
GM
Institute of Medical Biochemistry, University of Graz, Austria.
Grillhofer
H
H
D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism; D017270:Lipoprotein(a) / Q000302:isolation & purification / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000378:metabolism*; D012867:Skin / Q000378:metabolism
D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol