Cellular binding and degradation of lipoprotein (a).
Lp(a) is an important contributing factor to the development of atherosclerosis, and in structure is similar to LDL. Given the central role of the LDL receptor (LDL-R) in the metabolism of LDL, we felt that a study of the binding and degradation of Lp(a) facilitated by the LDL-R of human monocyte derived macrophages (HMDM) would be of value in understanding its pathological nature. In this study we compared equimolar amounts of Lp(a) and LDL and found that nearly equal amounts of Lp(a) and LDL bound to the LDL-R of HMDM at 4 degrees C, however the affinity of both lipoproteins was much lower than has been observed for the LDL-R of fibroblasts, being 0.80 muM for Lp(a) and 0.23 muM for LDL. The binding of Lp(a) to HMDM could be competed by 63% with a 50-fold excess of LDL. Degradation of Lp(a) at 37 degree C, unlike 4 degrees C binding, was mainly nonspecific (75% of total Lp(a) degradation) and when compared on an equimolar basis, nearly 6 times more LDL than Lp(a) was processed by the LDL-R pathway in 5 hr. Lower degradation of Lp(a) appears to be the result of lower binding at 37 degree C and a lower degradation rate when compared to LDL. It was not caused by increased intracellular accumulation or retroendocytosis. Degradation of both lipoproteins was only modestly affected by up and down regulation of the LDL-R. Because the binding of LDL at 4 degrees C and degradation at 37 degree C is mainly LDL-R specific, whereas only the 4 degree C binding of Lp(a) is so, suggests that the poor LDL-R dependent degradation of Lp(a) at 37 degree C is caused by a conformational change that is inducted in Lp(a) upon lowering the temperature to 4 degree C which allows better recognition of Lp(a) by the HMDM LDL-R.
Fless
G M
GM
University of Chicago IL 60637 USA.
D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D013696:Temperature
D017270:Lipoprotein(a); D011973:Receptors, LDL