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Low density lipoprotein oxidation and atherosclerosis


School of Biological Sciences

Applications accepted all year round Self-Funded PhD Students Only

About the Project

"The research in Professor David Leake’s group is concerned with atherosclerosis, the underlying cause of
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."

References

Wen, Y. & Leake, D.S. (2007) Circ. Res. 100, 1337-1343. Low density lipoprotein undergoes
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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