Christoffersen Group - Lipoprotein and atherosclerosis

The biological role of apolipoprotein M.

Apolipoproteins (apo's) are plasma proteins associated with lipoprotein particles. They serve as solubilizers of plasma lipids, platform for enzymatic reactions and ligands for cellular receptors. ApoM is mainly associated with HDL. We have generated genetically modified mouse models that either overexpress apoM or lack the apoM gene (apoM-knock out mice) and use these models to unravel the biology of apoM. Our studies have revealed that apoM is an important carrier of sphingosine-1-phosphate (S1P). The apoM/S1P complex have impact on atherosclerosis, heart failure, energy metabolism and the blood brain barrier. We are currently exploring the mechanisms in close collaborations with groups in Sweden, USA, Switzerland and Austria.

Classical atherosclerosis

Atherosclerosis in the underlying cause of ~90 % of cardiovascular deaths in the western world. We use cell cultures, human tissue biopsies collected at Rigshospitalet, and various mouse models to study basic mechanisms in atherosclerosis.

Kidney disease and cardiovascular health

Chronic kidney disease leads to accumulation of waster products in plasma (uremia). During recent years it has become clear that patients with chronic kidney disease has an enormously increased risk of dying from cardiovascular disease. We have in close collaboration with clinicians at the Department of Nephrology at Rigshospitalet established a unique human cohort and biobank with 1000 patients with chronic kidney disease. These will together with our animal models be used to study the pathogenesis of uremic atherosclerosis and cardiovascular disease.

Further, one of the main causes of uremia is renal fibrosis. No good biomarkers of renal fibrosis is available and the mechanistic insight is limited. We are currently establishing a biobank of plasma samples and kidney biopsies to search for such mechanistic links.

Cardiac disease in diabetes and obesity

Diabetes and obesity can decrease heart function. We are interested in exploring the role of cardiac lipid accumulation. We have used human heart biopsies, a cardiac cell line and various obese and genetically modified mouse models to disclose how the ability of the heart to secrete lipoproteins can protect against development of cardiac dysfunction. In addition, we are interested in how diabetes and obesity affect the cardiac metabolism of natriuretic peptides.