Research Groups > Genes and Metabolism Lipoprotein

The aim of the Lipoprotein Group is to understand the genetic mechanisms that regulate the metabolism of lipoproteins in the blood circulation. A raised concentration of cholesterol in plasma is a major risk factor for premature atherosclerosis, leading to coronary heart disease, which is the leading cause of chronic illness and early death in Western societies, and is now becoming more prevalent in less developed countries. Identifying the genes that are defective in individuals with inherited hypercholesterolaemia allows early identification of affected relatives, and understanding the mechanisms involved may reveal new strategies for lipid-lowering therapy.

Fig 1. Autosomal recessive hypercholesterolaemia (ARH; click on image to enlarge)

ARH functions as specific adaptor for the LDL receptor, allowing its internalisation via clathrin-coated pits. Most cells that lack ARH are unable to internalise the LDL receptor, but uptake is normal in human skin fibroblasts in culture, where another adaptor protein, Dab 2, may substitute.

Fig 2. How does PCSK9 reduce LDL receptor protein? (click on image to enlarge)