Dataset Information

Anti-?2GPI antibodies stimulate endothelial cell microparticle release via a nonmuscle myosin II motor protein-dependent pathway.

ABSTRACT: The antiphospholipid syndrome is characterized by thrombosis and recurrent fetal loss in patients with antiphospholipid antibodies (APLAs). Most pathogenic APLAs are directed against ?2-glycoprotein I (?2GPI), a plasma phospholipid binding protein. One mechanism by which circulating antiphospholipid/anti-?2GPI antibodies may promote thrombosis is by inducing the release of procoagulant microparticles from endothelial cells. However, there is no information available concerning the mechanisms by which anti-?2GPI antibodies induce microparticle release. In seeking to identify proteins phosphorylated during anti-?2GPI antibody-induced endothelial activation, we observed phosphorylation of nonmuscle myosin II regulatory light chain (RLC), which regulates cytoskeletal assembly. In parallel, we observed a dramatic increase in the formation of filamentous actin, a two- to fivefold increase in the release of endothelial cell microparticles, and a 10- to 15-fold increase in the expression of E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and tissue factor messenger RNA. Microparticle release, but not endothelial cell surface E-selectin expression, was blocked by inhibiting RLC phosphorylation or nonmuscle myosin II motor activity. These results suggest that distinct pathways, some of which mediate cytoskeletal assembly, regulate the endothelial cell response to anti-?2GPI antibodies. Inhibition of nonmuscle myosin II activation may provide a novel approach for inhibiting microparticle release by endothelial cells in response to anti-?2GPI antibodies.

SUBMITTER: Betapudi V

PROVIDER: S-EPMC3843239 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Anti-β2GPI antibodies stimulate endothelial cell microparticle release via a nonmuscle myosin II motor protein-dependent pathway.

Betapudi Venkaiah V Lominadze George G Hsi Linda L Willard Belinda B Wu Meifang M McCrae Keith R KR

Blood 20130816 23

The antiphospholipid syndrome is characterized by thrombosis and recurrent fetal loss in patients with antiphospholipid antibodies (APLAs). Most pathogenic APLAs are directed against β2-glycoprotein I (β2GPI), a plasma phospholipid binding protein. One mechanism by which circulating antiphospholipid/anti-β2GPI antibodies may promote thrombosis is by inducing the release of procoagulant microparticles from endothelial cells. However, there is no information available concerning the mechanisms by ...[more]

PMID: 23954892

Similar Datasets

Project description:Endothelial cell dysfunction plays a fundamental role in the pathogenesis of atherosclerosis (AS), and endothelial autophagy has protective effects on the development of AS. Our previous study had shown that oxidized low-density lipoprotein/β2-glycoprotein I/anti-β2-glycoprotein I antibody (oxLDL/β2GPI/anti-β2GPI) complex could promote the expressions of inflammatory cytokines and enhance the adhesion of leukocytes to endothelial cells. In the present study, we aimed to assess the effects of oxLDL/β2GPI/anti-β2GPI complex on endothelial autophagy and explore the associated potential mechanisms. Human umbilical vein endothelial cells (HUVECs) and mouse brain endothelial cell line (bEnd.3) were used as models of the vascular endothelial cells. Autophagy was evaluated by examining the expressions of autophagic proteins using western blotting analysis, autophagosome accumulation using transmission electron microscopy, and RFP-GFP-LC3 adenoviral transfection and autophagic flux using lysosome inhibitor chloroquine. The expressions of phospho-PI3K, phospho-AKT, phospho-mTOR, and phospho-eNOS were determined by western blotting analysis. 3-Methyladenine (3-MA) and rapamycin were used to determine the role of autophagy in oxLDL/β2GPI/anti-β2GPI complex-induced endothelial cell dysfunction. We showed that oxLDL/β2GPI/anti-β2GPI complex suppressed the autophagy, evidenced by an increase in p62 protein, a decrease in LC3-II and Beclin1, and a reduction of autophagosome generation in endothelial cells. Moreover, inhibition of autophagy was associated with PI3K/AKT/mTOR and eNOS signaling pathways. Rapamycin attenuated oxLDL/β2GPI/anti-β2GPI complex-induced endothelial inflammation, oxidative stress, and apoptosis, whereas 3-MA alone induced the endothelial injury. Our results suggested that oxLDL/β2GPI/anti-β2GPI complex inhibited endothelial autophagy via PI3K/AKT/mTOR and eNOS signaling pathways and further contributed to endothelial cell dysfunction. Collectively, our findings provided a novel mechanism for vascular endothelial injury in AS patients with an antiphospholipid syndrome (APS) background.

Dataset Information

Anti-?2GPI antibodies stimulate endothelial cell microparticle release via a nonmuscle myosin II motor protein-dependent pathway.

Publications

Anti-β2GPI antibodies stimulate endothelial cell microparticle release via a nonmuscle myosin II motor protein-dependent pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure