A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma.
Oxidized phospholipids (OxPLs) on apolipoprotein B-100 (apoB-100) particles are strongly associated with lipoprotein [a] (Lp[a]). In this study, we evaluated whether Lp[a] is preferentially the carrier of OxPL in human plasma. The content of OxPL on apoB-100 particles was measured with monoclonal antibody E06, which recognizes the phosphocholine (PC) headgroup of oxidized but not native phospholipids. To assess whether OxPLs were preferentially bound by Lp[a] as opposed to other lipoproteins, immunoprecipitation and ultracentrifugation experiments, in vitro transfer studies, and chemiluminescent ELISAs were performed. Immunoprecipitation of Lp[a] from human plasma with an apolipoprotein [a] (apo[a])-specific antibody demonstrated that more than 85% of E06 reactivity (i.e., OxPL) coimmunoprecipitated with Lp[a]. Ultracentrifugation experiments showed that nearly all OxPLs were found in fractions containing apo[a], as opposed to other apolipoproteins. In vitro transfer studies showed that oxidized LDL preferentially donates OxPLs to Lp[a], as opposed to LDL, in a time- and temperature-dependent manner, even in aqueous buffer. Approximately 50% of E06 immunoreactivity could be extracted from isolated Lp[a] following exposure of plasma to various lipid solvents. These data demonstrate that Lp[a] is the preferential carrier of PC-containing OxPL in human plasma. This unique property of Lp[a] suggests novel insights into its physiological function and mechanisms of atherogenicity.
Bergmark
Claes
C
Department of Vascular Surgery, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
Dewan
Asheesh
A
Orsoni
Alexina
A
Merki
Esther
E
Miller
Elizabeth R
ER
Shin
Min-Jeong
MJ
Binder
Christoph J
CJ
Hörkkö
Sohvi
S
Krauss
Ronald M
RM
Chapman
M John
MJ
Witztum
Joseph L
JL
Tsimikas
Sotirios
S
D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D017270:Lipoprotein(a) / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000097:blood* / Q000276:immunology / Q000378:metabolism*; D013379:Substrate Specificity; D014461:Ultracentrifugation
D017270:Lipoprotein(a); D010743:Phospholipids