The oxidized phospholipids linked to human apolipoprotein(a) do not derive from circulating low-density lipoproteins and are probably of cellular origin.
Lipoprotein (a) [Lp(a)], a cardiovascular risk factor, is a low-density lipoprotein (LDL) variant shown to bind to oxidized phospholipids (oxPLs); however, its binding mode and origin have not been clearly established. We isolated both LDL and Lp(a) from the plasma of a population of high-Lp(a) subjects and in each Lp(a) particle separated apolipoprotein(a) [apo(a)], from the LDL component, Lp(a(-)). These products were assayed by an ELISA using monoclonal antibody T15 with a known specificity for oxPLs. In each subject, the T15 reactivity was confined to apo(a). Moreover, the amount of oxPL bound to apo(a) was unaffected by plasma Lp(a) levels and apo(a) size polymorphism. We have previously shown that kringle V (KV) is the site of oxPL linkage in human apo(a). In this work, we expressed in human embryonic kidney cells a KV-containing recombinant that, when purified from the medium, contained oxPLs. In summary, in human plasma Lp(a), the oxPLs are located in apo(a) and not in the circulating LDLs, suggesting a cellular origin. This latter concept is supported by the studies in which an expressed KV-containing apo(a) microdomain exhibited oxPL reactivity. Thus, apo(a) can undergo potentially pathogenic posttranslational modifications in a cellular environment able to generate oxPL.
Edelstein
Celina
C
University of Chicago, Department of Medicine, 5841 S. Maryland Ave, Chicago, IL 60637, USA.
Philips
Binu
B
Pfaffinger
Ditta
D
Scanu
Angelo M
AM
D000328:Adult; D000368:Aged; D053241:Apoprotein(a) / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D018082:Kringles; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D008077:Lipoproteins, LDL; D010743:Phospholipids; D053241:Apoprotein(a)