Lisanne Blauw, PhD

Cardiovascular diseases are the number one cause of death worldwide. My research is centred on the role of lipid and energy metabolism in cardiovascular disease development, with a specific interest in lipoprotein lipase (LPL) and fatty acid metabolism.

During my PhD I focussed on genetic determinants of lipid and energy metabolism with a specific interest in cholesteryl ester transfer protein (CETP), a circulating protein that is able to induce a proatherogenic lipoprotein profile. Therefore, a reduction in CETP activity was proposed as a strategy to improve the lipoprotein profile and reduce cardiovascular disease. However, using a Mendelian randomization approach, we showed that CETP is only marginally associated with cardiovascular disease and affects mainly high-density lipoprotein (HDL) particles rather than the pro-atherogenic low-density lipoprotein (LDL) particles. This is in line with the disappointing results of four clinical trials with CETP inhibitors, showing no or only small beneficial effects on cardiovascular risk reduction. As such, we have to reconsider the role of CETP in cardiovascular disease.

More recently, the enzyme LPL has gained a lot of attention as novel druggable target for cardiovascular risk reduction. My Postdoc research is directed at LPL and its function in lipid metabolism and cardiovascular disease. LPL plays a key role in energy metabolism by supplying metabolically active tissues with fuel in the form of fatty acids. Triglycerides derived from the core of triglyceride-rich lipoproteins (TRL) are hydrolysed by LPL into free fatty acids, which are subsequently taken up by energy-demanding tissues, while the generated pro-atherogenic TRL remnants are avidly taken up by the liver. Pharmacologically increasing LPL activity is therefore thought to be a promising way to reduce atherosclerosis development. I have been redirecting my research focus from genetic epidemiology towards the area of biomedical engineering, specifically human induced pluripotent stem cell (hiPSC)-derived organ-on-chip models in the cardiac field. I started a collaboration with the group of Prof. Robert Passier, Applied Stem Cell Technologies, University of Twente, to study hiPSC endothelial-cardiomyocyte crosstalk on a 3D heart-on-chip model.