| Our research focuses on various genetic predispositions of developing premature atherosclerotic (cardio)vascular disease. We are specifically interested in cholesterol metabolism (both 'bad' cholesterol, i.e. LDL cholesterol, as well as 'good' cholesterol, i.e. HDL cholesterol), triglyceride metabolism, and interactions between DNA and cholesterol-lowering drugs. In a specialized outpatient clinic, patients with genetic dyslipidemias and premature vascular disease are seen and treated. These patients provide the basis for a large part of the following research.We investigate patients with familial hypercholesterolemia (FH). Due to mutations in low-density lipoprotein receptor gene, plasma cholesterol levels in these patients are elevated thereby increasing the risk of a cardiovascular event. We work on the improvement of disease management: from case finding, diagnosis, treatment, follow-up, and in the future, cure by gene therapy. Additionally, genetic modifiers, modulating the expression of FH are assessed in each patient to more accurately tailor therapy to the patient's specific requirements.Secondly, we are developing gene therapy strategies to improve the phenotype of patients who suffer from high levels of plasma triglycerides due to mutations in the lipoprotein lipase gene. These patients have an increased risk for potentially lethal pancreatitis. For this purpose, we will use viral vectors that will also serve in fundamental research as a tool to obtain better insight into triglyceride metabolism.A third project concentrates on the interactions between specific mutations in the DNA of cardiovascular patients and cholesterol-lowering drugs. Finally, we conduct studies into the genetic background of both low and high levels of HDL cholesterol. This will hopefully serve the development of a new series of drugs that can raise this type of cholesterol, in order to prevent or regress coronary atherosclerosis. |
