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Decreased low-density lipoprotein oxidation after repeated selective apheresis in homozygous familial
C Napoli1, G Ambrosio, N Scarpato
1Department of Clinical and Experimental Medicine, Federico II School of Medicine, University of Naples, Italy.
Insights
Selective LDL apheresis reduces mortality in familial hypercholesterolemia by decreasing LDL levels and making LDL less susceptible to oxidation, potentially slowing coronary atherosclerosis.
Area of Science:
- Cardiovascular Genetics
- Lipid Metabolism
- Atherosclerosis Research
Background:
- Familial hypercholesterolemia (FH) is a genetic disorder causing early myocardial infarction.
- Homozygous FH patients exhibit rapid coronary atherosclerosis and high mortality.
- Low-density lipoprotein (LDL) accumulation and oxidation are key in FH atherogenesis.
Purpose of the Study:
- To investigate changes in LDL oxidation in homozygous FH patients undergoing LDL apheresis.
- To assess the impact of repeated LDL apheresis on LDL's susceptibility to oxidation.
Main Methods:
- Studied eight homozygous FH patients undergoing selective LDL apheresis.
- Measured LDL lipid peroxidation (conjugated dienes, lipid peroxides, malondialdehyde).
- Assessed oxidative indexes of LDL's protein moiety (ApoB-100 fragmentation, TNBS reactivity, electrophoresis mobility).
Main Results:
- Repeated LDL apheresis increased LDL's resistance to oxidation.
- Oxidative indexes of the LDL protein moiety showed reduced oxidation.
- Cholesteryl esterification within LDL decreased post-apheresis.
Conclusions:
- Selective LDL apheresis reduces LDL levels and enhances LDL's resistance to oxidation.
- This reduced susceptibility to oxidation may contribute to decreased coronary atherosclerosis and mortality in FH patients.
Abstract:
Familial hypercholesterolemia was the first genetic disorder recognized to cause myocardial infarction. Patients with homozygous familial hypercholesterolemia have rapidly progressive coronary atherosclerosis with angina pectoris, myocardial infarction, or sudden death at a young age. Selective apheresis on dextran sulfate cellulose columns reduces mortality and may induce regression of coronary lesions. These patients have both increased levels and prolonged circulation residence time of low-density lipoprotein (LDL), which is not removed by cellular receptor. LDL oxidation may play a pivotal role in atherogenesis. LDL undergoes oxidation before being taken up by macrophages and then transformed into arterial wall foam cells. The aim of this study was to investigate LDL oxidation in eight homozygous patients with familial hypercholesterolemia during repeated LDL apheresis. LDL lipid peroxidation, estimated by conjugated-diene absorbance at 234 nm, lipid peroxides, and malondialdehyde showed an increased resistance against oxidation after repeated LDL apheresis. This phenomenon was also observed in the oxidative indexes of protein moiety of LDL (apolipoprotein-B100 fragmentation, trinitrobenzenesulfonic acid reactivity, and electrophoresis agarose mobility). Similarly, cholesteryl esterification was decreased after LDL apheresis. Thus selective LDL apheresis not only decreases the pool of LDL, but it also induces changes that render LDL less susceptible to oxidation. This phenomenon might contribute to reduce coronary atherosclerosis and thus mortality of these particular patients.