Identification and analyses of inhibitors targeting apolipoprotein(a) kringle domains KIV-7, KIV-10, and KV provide insight into kringle domain function
Jenny Sandmark, Anna Tigerström, Tomas Åkerud, Magnus Althage, Thomas Antonsson, Stefan Blaho, Cristian Bodin, Jonas Boström, Yantao Chen, Anders Dahlén, Per‐Olof Eriksson, Emma Evertsson, Tomas Fex, Ola Fjellström, David Gustafsson, Margareta Herslöf, Ryan Hicks, Emelie Jarkvist, Carina Johansson, I. Kalies, Birgitta Karlsson Svalstedt, Fredrik Kartberg, Anne Legnehed, Sofia Martinsson, Andreas Moberg, Marianne Ridderström, Birgitta Rosengren, Alan Sabirsh, Anders Thelin, Johanna Vinblad, Annika Wellner, Bingze Xu, Ann‐Margret Östlund‐Lindqvist, Wolfgang Knecht
Abstract
assays. These assays revealed the assembly of Lp(a) from apo(a) and LDL, as well as potential pathophysiological mechanisms of Lp(a), including (i) binding to fibrin, (ii) stimulation of smooth-muscle cell proliferation, and (iii) stimulation of LDL uptake into differentiated monocytes. Our results indicate that a small-molecule inhibitor targeting the lysine-binding site of KIV-10 can combat the pathophysiological effects of Lp(a).