Triglyceride-rich Lipoproteins and Cardiovascular Disease

It is well established that hypercholesterolaemia is causatively linked to cardiovascular disease (CVD) and that lowering of cholesterol levels reduces CVD events. However, cholesterol-lowering medication only prevents up to half of these events.

Recent advances in human genetics indicate that the remaining ‘residual’ risk of CVD is caused by elevated levels of triglyceride-rich lipoproteins and their remnants. These particles are not efficiently lowered by today’s cholesterol-lowering medications.

The overall aim of this proposal is to understand the underlying mechanisms and consequences of impaired lipid metabolism in humans with the goal of translating this knowledge into the clinic.

Very few detailed kinetic studies of this type have been undertaken because they are technically challenging and most centres lack access to the rare study subjects.

CVD prevention is about to enter an era of precision medicine where treatments are tailored to each patient to provide optimum, cost-effective benefit for different types of increased blood lipids, and studies like ours are important to develop effective treatment strategies for individuals with hypertriglyceridemia beyond cholesterol lowering.

We will also resolve the atherogenicity of triglyceride-rich lipoproteins (TRLs), and decipher novel pathways that regulate hepatic biogenesis of TRLs as this has profound implications for understanding the pathophysiology of hypertriglyceridemia.