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Plasma lipoproteins and monocyte-macrophages in a peroxisome-deficient system: study of a patient with infantile
Abstract:
Hypocholesterolaemia in infantile Refsum disease (IRD) may link peroxisomes and lipoprotein metabolism. In our patient, plasma cholesterol levels were reduced to 26% and 29% of control in LDL and HDL fractions, respectively. Plasma apolipoproteins B-100 and A-I levels were 52% and 66% of controls, respectively. In the kindred, plasma cholesterol concentration was 61-73% of controls. The HDL-cholesterol/apo A-I ratios were: patient 0.12; kindred 0.17; controls 0.28. Analysis of the IRD patient's lipoprotein revealed compositional abnormalities in all fractions. The patient's LDL demonstrated a substantial reduction in its lipid-to-protein ratio. Alterations in plasma lipoproteins affect their interaction with macrophages. Upon incubation of the patient's LDL with J-774 macrophages, its cellular uptake, measured as cholesterol esterification rate, was only 66% of a control rate. The abnormal LDL of the IRD patient showed also only 25% of control susceptibility to in vitro oxidation. Studies of cellular cholesterol metabolism in the patient's monocyte-derived macrophages (MDM) showed 57% increased cholesterol esterification rate in comparison to normal MDM. The possible link between lipoprotein abnormalities and monocyte-macrophage cholesterol metabolism is discussed.
Insights
Infantile Refsum disease (IRD) causes hypocholesterolaemia, altering lipoprotein composition and macrophage cholesterol metabolism. This study investigates the link between peroxisomal dysfunction and lipid abnormalities in IRD patients.
Area of Science:
- Biochemistry
- Cell Biology
- Genetics
Background:
- Infantile Refsum disease (IRD) is a peroxisomal disorder.
- Lipoprotein metabolism and peroxisomal function may be linked.
- Hypocholesterolaemia is observed in IRD patients.
Observation:
- IRD patients exhibit significantly reduced plasma cholesterol levels in LDL and HDL fractions.
- Apolipoprotein B-100 and A-I levels are decreased in IRD patients.
- Lipoprotein compositional abnormalities, including reduced lipid-to-protein ratio in LDL, are present in IRD.
Findings:
- Patient-derived LDL shows reduced cellular uptake by macrophages (66% of control).
- IRD LDL exhibits decreased susceptibility to in vitro oxidation (25% of control).
- Monocyte-derived macrophages (MDM) from IRD patients show increased cholesterol esterification (57% higher than controls).
Implications:
- Lipoprotein abnormalities in IRD impact their interaction with macrophages.
- Altered cholesterol metabolism in macrophages of IRD patients may contribute to disease pathogenesis.
- Further research is needed to elucidate the complex interplay between peroxisomes, lipoproteins, and cellular cholesterol handling in IRD.