Lipoprotein(a) mediates high affinity low density lipoprotein association to receptor negative fibroblasts.
Lipoprotein(a) (Lp(a)) is an acute phase protein with unknown function. Lp(a) binds to low density lipoprotein (LDL) receptors, as well as to plasminogen (Plg) receptors. Preincubation of normal human skin fibroblasts with Lp(a) or with apo(a) cause a severalfold increase of LDL binding. Plg and kringle-4 of Plg have no effect. LDL receptor-negative fibroblasts respond upon preincubation with apo(a) with high affinity binding of LDL with Kd values that are almost identical with those of LDL binding to the LDL receptor. Incubation of apo(a)-pretreated fibroblasts with anti-apo(a) completely abolishes the increment of LDL binding. The high affinity LDL binding to LDL receptor-negative fibroblasts could be dissociated by approximately 80 and 54% with 5 mg/ml proline and 30 mg/ml NaCl, respectively, but not with dextran sulfate. The Lp(a)- and apo(a)-triggered LDL binding to fibroblasts have no effect on LDL internalization. These findings may reflect a key function in the role as an acute phase protein and may be relevant to the high atherogeneicity of Lp(a).
Kostner
G M
GM
Institute of Medical Biochemistry, University of Graz, Austria.
Grillhofer
H K
HK
D001053:Apolipoproteins / Q000378:metabolism*; D053241:Apoprotein(a); D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology; D008854:Microscopy, Electron; D011973:Receptors, LDL / Q000378:metabolism
D001053:Apolipoproteins; D008024:Ligands; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol; D008148:Lovastatin; D053241:Apoprotein(a)