Dynamics of dense electronegative low density lipoproteins and their preferential association with lipoprotein phospholipase A(2).
Small, dense, electronegative low density lipoprotein [LDL(-)] is increased in patients with familial hypercholesterolemia and diabetes, populations at increased risk for coronary artery disease. It is present to a lesser extent in normolipidemic subjects. The mechanistic link between small, dense LDL(-) and atherogenesis is not known. To begin to address this, we studied the composition and dynamics of small, dense LDL(-) from normolipidemic subjects. NEFA levels, which correlate with triglyceride content, are quantitatively linked to LDL electronegativity. Oxidized LDL is not specific to small, dense LDL(-) or lipoprotein [a] (i.e., abnormal lipoprotein). Apolipoprotein C-III is excluded from the most abundant LDL (i.e., that of intermediate density: 1.034 < d < 1.050 g/ml) but associated with both small and large LDL(-). In contrast, lipoprotein-associated phospholipase A(2) (LpPLA(2)) is highly enriched only in small, dense LDL(-). The association of LpPLA(2) with LDL may occur through amphipathic helical domains that are displaced from the LDL surface by contraction of the neutral lipid core.
Gaubatz
John W
JW
Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Gillard
Baiba K
BK
Massey
John B
JB
Hoogeveen
Ron C
RC
Huang
Max
M
Lloyd
Eric E
EE
Raya
Joe L
JL
Yang
Chao-Yuh
CY
Pownall
Henry J
HJ
D053305:Apolipoprotein C-III / Q000032:analysis; D004563:Electrochemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005230:Fatty Acids, Nonesterified / Q000737:chemistry; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D054467:Phospholipases A2 / Q000378:metabolism*; D011485:Protein Binding; D055672:Static Electricity
D053305:Apolipoprotein C-III; D005230:Fatty Acids, Nonesterified; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D054467:Phospholipases A2