Electronegative LDL of FH subjects: chemical characterization and induction of chemokine release from human endothelial cells.
Electronegative LDL (LDL(-)) constitutes a plasma subfraction of LDL with proinflammatory properties. Its proportion is increased in familial hypercholesterolemia (FH); however, the characteristics of LDL(-) isolated from FH subjects have not been previously studied. In this work, the composition, oxidative status, and inflammatory capacity on endothelial cells of LDL(-) from FH and normolipemic (NL) subjects were evaluated. LDL(-) from FH was relatively enriched in esterified and free cholesterol and triglyceride, and had lower apoB and phospholipid content compared with the non-electronegative fraction (LDL(+)). LDL(-) also contained increased amounts of apoE, apoC-III, sialic acid, and non-esterified fatty acids (NEFAs). The same was observed in NL subjects, except that esterified cholesterol and phospholipid were similar in LDL(-) and LDL(+). No difference was observed between the two fractions concerning malondialdehyde, fatty acid hydroxides, and antioxidants, thereby indicating the absence of increased oxidation of LDL(-) compared with LDL(+). When LDL(-) (100 mg/l) from NL and FH subjects was incubated for 24 h with human umbilical vein endothelial cells (HUVECs), interleukin 8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) increased twofold in the culture medium compared with LDL(+). Vascular cell adhesion molecule 1 (VCAM-1) expression was not increased by LDL(-). Our data indicate that LDL(-) from FH or NL subjects shows no evidence of increased oxidative modification compared to LDL(+); however, LDL(-) induces twofold the release of chemokines by endothelial cells. This effect, which may contribute to leukocyte recruitment and promote atherogenesis, may be greater in FH subjects in which LDL(-) can be up to eightfold higher than in NL subjects.
Sánchez-Quesada
José Luis
JL
Servei de Bioquímica del Hospital de la Santa Creu i Sant Pau (HSCSP), C/Antoni Maria Claret 167, 08025 Barcelona, Spain.
Camacho
Mercedes
M
Antón
Rosa
R
Benítez
Sonia
S
Vila
Lluis
L
Ordóñez-Llanos
Jordi
J
D015153:Blotting, Western; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis; D004730:Endothelium, Vascular / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000503:physiopathology*; D016209:Interleukin-8 / Q000032:analysis; D008077:Lipoproteins, LDL / Q000032:analysis* / Q000737:chemistry*; D011336:Probability; D012016:Reference Values; D018709:Statistics, Nonparametric; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis*
D018932:Chemokine CCL2; D016209:Interleukin-8; D008077:Lipoproteins, LDL; D019010:Vascular Cell Adhesion Molecule-1