About the Project
coronary heart disease and strokes. We are investigating how low density lipoprotein (LDL), which
carries most of the cholesterol in blood, is oxidised (i.e. becomes ‘rancid’) and the damaging effects
that oxidised LDL has on arterial cells. Atherosclerotic lesions are inflammatory sites and contain
many macrophages. We have shown that LDL is oxidised within lysosomes in macrophages
and that this oxidation is catalysed by iron at the lysosomal pH of 4.5. The ultimate aim is to use
antioxidants targetted to lysosomes in humans to prevent atherosclerosis."
oxidation within lysosomes in cells
Satchell, L. & Leake, D.S. (2012) Biochemistry 51, 3767-3775. Oxidation of low-density lipoprotein
by iron at lysosomal pH: Implications for atherosclerosis
Ahmad, F. & Leake, D.S. (2018) Chem. Phys. Lipids 213, 13-24. Antioxidants inhibit low density
lipoprotein oxidation less at lysosomal pH: A possible explanation as to why the clinical trials of
antioxidants might have failed
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