Peter Carmeliet is Professor at the Katholieke Universiteit Leuven and Adjunct Director of the VIB Vesalius Research Center, KU Leuven, Belgium. He is internationally renowned for his research on the growth and functioning of blood vessels, with key findings including identification of which signalling molecules play a role in the formation of new blood vessels, as well as investigation of vascular growth in tumours. His research interests also include investigating the molecular basis of endothelial cell dysfunction and regeneration. Professor Carmeliet was awarded the 2018 Heineken Prize for Medicine for his pioneering research on blood vessel formation, elected a foreign member of the Royal Netherlands Academy of Arts and Sciences in 2017, and the recipient of the 2016 Anitschkow Award from the European Atherosclerosis Society.
Monday 27 May 08:30
Metabolic heterogeneity of endothelial cells in CVD
Endothelial cells are critical to the regulation of organ growth, regeneration and stem cell function and therefore play a key role in the pathophysiology of diseases such as atherosclerosis, diabetes and hypertension. Within the same organ, endothelial cells may have different origins, heterogeneous properties and functional specialization. Distinct gene expression patterns influence the function of endothelial cells including their angiogenic potential, together with the tissue environment and epigenetic factors.
Insights into endothelial metabolism have indicated the importance of glycolysis, a key metabolic pathway, in the regulation of endothelial cell function. Other pathways have also been implicated, including fatty acid oxidation and, more recently, glutamine/asparagine metabolism. Targeting endothelial cell metabolism and metabolic crosstalk may therefore offer a means of limiting oxidative stress and hyperglycaemia-induced endothelial dysfunction that underpin the development of diabetes-related vascular complications. However, as hyperglycaemia-induced endothelial cell dysfunction varies across different vascular beds, and diabetes preferentially affects endothelial cells in some but not in all vascular beds, further study is needed. Investigation of the consequences of over- or underexpression of a specific target in endothelial cells could ultimately provide future therapeutic potential.
Eelen G, Dubois C, Cantelmo A, Goveia J, Brüning U, DeRan M, Jarugumilli G, van Rijssel J, Saladino G, Comitani F, Zecchin A, Rocha S, Chen R, Huang H, Vandekeere S, Kalucka J, Lange C, Morales-Rodriguez F, Cruys B, Treps L, Ramer L, Vinckier S, Brepoels K, Wyns S, Souffreau J, Schoonjans L, Lamers WH, Wu Y, Haustraete J, Hofkens J, Liekens S, Cubbon R, Ghesquière B, Dewerchin M, Gervasio FL, Li X, van Buul JD, Wu X, Carmeliet P. Role of glutamine synthetase in angiogenesis beyond glutamine synthesis. Nature 2018;561:63-9.
Kalucka J, Bierhansl L, Conchinha NV, Missiaen R, Elia I, Brüning U, Scheinok S, Treps L, Cantelmo AR, Dubois C, de Zeeuw P, Goveia J, Zecchin A, Taverna F, Morales-Rodriguez F, Brajic A, Conradi LC, Schoors S, Harjes U, Vriens K, Pilz GA, Chen R, Cubbon R, Thienpont B, Cruys B, Wong BW, Ghesquière B, Dewerchin M, De Bock K, Sagaert X, Jessberger S, Jones EAV, Gallez B, Lambrechts D, Mazzone M, Eelen G, Li X, Fendt SM, Carmeliet P. Quiescent endothelial cells upregulate fatty acid β-oxidation for vasculoprotection via redox homeostasis. Cell Metab 2018; doi: 10.1016/j.cmet.2018.07.016. [Epub ahead of print]
Bruning U, Morales-Rodriguez F, Kalucka J, Goveia J, Taverna F, Queiroz KCS, Dubois C, Cantelmo AR, Chen R, Loroch S, Timmerman E, Caixeta V, Bloch K, Conradi LC, Treps L, Staes A, Gevaert K, Tee A, Dewerchin M, Semenkovich CF, Impens F, Schilling B, Verdin E, Swinnen JV, Meier JL, Kulkarni RA, Sickmann A, Ghesquière B, Schoonjans L, Li X, Mazzone M, Carmeliet P. Impairment of angiogenesis by fatty acid synthase inhibition involves mTOR malonylation. Cell Metab 2018; doi: 10.1016/j.cmet.2018.07.019. [Epub ahead of print]