Macrophage lipoprotein lipase expression is increased in patients with heterozygous familial hypercholesterolemia.
FH is associated with accelerated atherosclerosis. Based on the crucial role of macrophage LPL in atherogenesis, we determined in the present study macrophage LPL expression in patients with FH. Monocytes isolated from 13 FH patients and 13 control subjects were differentiated into macrophages by culturing the cells for 9 days in 20% autologous or heterologous serum. Macrophages of patients with FH cultured in their own sera showed a significant increase in LPL mRNA levels, extracellular LPL mass, and activity compared with macrophages of control subjects. Although these alterations positively correlated with the levels of serum platelet-derived growth factor-BB (PDGF-BB) in FH subjects, increased LPL secretion by cultured FH macrophages was reduced neither by immunoneutralizing FH serum with an anti-PDGF-BB antibody, nor by culturing these cells in sera from control subjects. With the exception of LPL, levels of other cytokines and 8-isoprostane were not increased in the supernatants of macrophages of FH patients. Serum from FH patients also enhances the levels of LPL secreted by macrophages from control subjects. Immunoneutralization of FH serum with an anti-PDGF-BB antibody totally reversed this alteration. Overall, this study demonstrates that macrophages from FH subjects overproduce LPL and that PDGF present in the serum from FH patients stimulates LPL secretion by control macrophages. These findings suggest that macrophage LPL induction in patients with FH might be related to the increased atherogenesis observed in these subjects.
Beauchamp
Marie-Claude
MC
CHUM Research Centre and Metabolic Clinic, Notre-Dame Hospital, Montreal Quebec, Canada.
Letendre
Elaine
E
Renier
Geneviève
G
D000925:Anticoagulants / Q000032:analysis; D000077214:Becaplermin; D017077:Culture Media, Conditioned; D015237:Dinoprost / Q000031:analogs & derivatives*; D028441:F2-Isoprostanes / Q000032:analysis / Q000378:metabolism; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics / Q000378:metabolism*; D007118:Immunoassay; D007375:Interleukin-1 / Q000032:analysis / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000032:analysis*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D000925:Anticoagulants; D017077:Culture Media, Conditioned; D028441:F2-Isoprostanes; D007375:Interleukin-1; D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000077214:Becaplermin; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D008071:Lipoprotein Lipase