RT Journal Article
T1 Statins suppress apolipoprotein CIII-induced vascular endothelial cell activation and monocyte adhesion
A1 Azcutia Criado, Verónica
A1 Zheng, Chunyu
A1 Aikawa, Elena
A1 Figuereido, Jose-Luiz
A1 Croce, Kevin
A1 Sonoki, Hiroyuki
A1 Sacks, Frank M.
A1 Luscinskas, Francis W.
A1 Aikawa, Masanori
AB AimsActivation of vascular endothelial cells (ECs) contributes importantly to inflammation and atherogenesis. We previously reported that apolipoprotein CIII (apoCIII), found abundantly on circulating triglyceride-rich lipoproteins, enhances adhesion of human monocytes to ECs in vitro. Statins may exert lipid-independent anti-inflammatory effects. The present study examined whether statins suppress apoCIII-induced EC activation in vitro and in vivo.Methods and resultsPhysiologically relevant concentrations of purified human apoCIII enhanced attachment of the monocyte-like cell line THP-1 to human saphenous vein ECs (HSVECs) or human coronary artery ECs (HCAECs) under both static and laminar shear stress conditions. This process mainly depends on vascular cell adhesion molecule-1 (VCAM-1), as a blocking VCAM-1 antibody abolished apoCIII-induced monocyte adhesion. ApoCIII significantly increased VCAM-1 expression in HSVECs and HCAECs. Pre-treatment with statins suppressed apoCIII-induced VCAM-1 expression and monocyte adhesion, with two lipophilic statins (pitavastatin and atorvastatin) exhibiting inhibitory effects at lower concentration than those of hydrophilic pravastatin. Nuclear factor κB (NF-κB) mediated apoCIII-induced VCAM-1 expression, as demonstrated via loss-of-function experiments, and pitavastatin treatment suppressed NF-κB activation. Furthermore, in the aorta of hypercholesterolaemic Ldlr−/− mice, pitavastatin administration in vivo suppressed VCAM-1 mRNA and protein, induced by apoCIII bolus injection. Similarly, in a subcutaneous dorsal air pouch mouse model of leucocyte recruitment, apoCIII injection induced F4/80+ monocyte and macrophage accumulation, whereas pitavastatin administration reduced this effect.ConclusionsThese findings further establish the direct role of apoCIII in atherogenesis and suggest that anti-inflammatory effects of statins could improve vascular disease in the population with elevated plasma apoCIII.
PB Oxford Univ Press
YR 2013
FD 2013
LK https://hdl.handle.net/20.500.14352/116755
UL https://hdl.handle.net/20.500.14352/116755
LA eng
NO Zheng, Chunyu, et al. «Statins Suppress Apolipoprotein CIII-Induced Vascular Endothelial Cell Activation and Monocyte Adhesion». European Heart Journal, vol. 34, n.o 8, febrero de 2013, pp. 615-24. DOI.org (Crossref), https://doi.org/10.1093/eurheartj/ehs271
NO Kowa Company, Ltd (Tokyo, Japan)
NO National Heart, Lung and Blood Institute grants (EE.UU)
NO National Heart, Lung and Blood Institute grants (EE.UU)
NO American Heart Association
DS Docta Complutense
RD 10 abr 2025