PhD ceremony Ms. W. Annema: Understanding HDL function. Studies in preclinical models and patients

PhD ceremony: Ms. W. Annema, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Understanding HDL function. Studies in preclinical models and patients

Promotor(s): prof. U.J.F. Tietge

Faculty: Medical Sciences

High-density lipoprotein (HDL) function is a novel concept in cardiovascular research. The aim of the thesis was to provide more insight into the importance of HDL function for cardiovascular risk.

A key function of HDL in cardiovascular protection is reverse cholesterol transport (RCT). HDL-mediated macrophage-to-faeces RCT was markedly impaired in mice with lipopolysaccharide-induced acute inflammation. Moreover, in mice with type 1 diabetes mellitus RCT was reduced due to decreased selective uptake of HDL cholesteryl esters in the liver. Conversely, over-expression of apolipoprotein E, which has been associated with lower atherosclerosis in different mouse models, did not affect RCT from macrophages to faeces. Additional studies in patients showed that two key anti-atherogenic functionalities of HDL were impaired in patients with a severe acute myocardial infarction and this reduction in HDL function was related to increased plasma levels of myeloperoxidase in these patients. In addition, there was a positive association between the functionality of HDL and the function of pancreatic β-cells in patients with type 2 diabetes mellitus, suggesting that HDL function may contribute to the maintenance of β-cell function. Finally, prospective studies in renal transplant recipients showed that HDL cholesterol efflux function is not associated with cardiovascular and overall mortality but is a significant independent predictor of graft failure after kidney transplantation. In conclusion, although important information can be derived from assessment of HDL function over mere HDL cholesterol mass levels, large-scale prospective population-based studies are required to conclusively test a potential causal relationship between HDL function and disease.