Potent lipoprotein(a) lowering following apolipoprotein(a) antisense treatment reduces the pro-inflammatory activation of circulating monocytes in patients with elevated lipoprotein(a)

Lipoprotein(a) [Lp(a)] is a cholesterol-rich particle composed of a molecule of apolipoprotein B100 linked to a molecule of apolipoprotein(a). Lp(a) has been shown as crucial mediator of atherosclerosis and valvular calcification in the recent years and has only recently been subject of promising novel lipid-lowering agents. In this study, patients with cardiovascular diseases (CVD) received Lp(a) lowering agents including oligonucleotide therapy or PCSK9 antibody treatment. Antisense-treatment lowered Lp(a) levels to a much higher extent (47%) than PCSK9 antibody treatment (16%). In parallel, antisense-treatment reduced inflammatory gene expression and transendothelial migration in monocytes of CVD patients. However, PCSK9 administration did not change transcriptome nor migration properties of monocytes.  Altogether, Lp(a) emerges as promising target for the reduction of atherosclerosis and cardiovascular disease. Both PCSK9 antibody and apolipoprotein(a) antisense treatment show encouraging results for this purpose.