Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo

Citation
Ss. Pierangeli et al., Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo, CIRCULATION, 99(15), 1999, pp. 1997-2002
Citations number
46
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
00097322 → ACNP
Volume
99
Issue
15
Year of publication
1999
Pages
1997 - 2002
Database
ISI
SICI code
0009-7322(19990420)99:15<1997:AAFASP>2.0.ZU;2-A
Abstract
Background-Antiphospholipid (aPL) antibodies are associated with thrombosis in patients diagnosed with antiphospholipid syndrome (APS) and enhance thr ombus formation in vivo in mice, but the mechanism of thrombosis by aPL is not completely understood. Although aPL antibodies have been shown to inhib it protein C activation and activate endothelial cells (ECs) in vitro, no s tudy has examined whether these antibodies activate ECs in vivo. Therefore, human affinity-purified aPL (ap aPL) antibodies from APS patients were tes ted in a mouse model of microcirculation using the cremaster muscle that al lows direct microscopic examination of thrombus formation and adhesion of w hite blood cells (WBCs) to ECs as an indication of EC activation in vivo. A dhesion molecule expression on human umbilical vein endothelial cells (HUVE Cs) after aPL exposure was performed to confirm EC activation in vitro. Methods and Results-All 6 ap aPL antibodies significantly increased the exp ression of VCAM-1 (2.3- to 4.4-fold), with one of the antibodies also incre asing the expression of E-selectin (1.6-fold) on HUVECs in vitro. In the in vivo experiments, each ap aPL antibody except for I preparation increased WBC sticking (mean number of WBCs ranged from 22.7 to 50.6) compared with c ontrol (14.4), which correlated with enhanced thrombus formation (mean thro mbus size ranged from 1098 to 6476 versus 594 mu m(2) for control). Conclusions-Activation of ECs by aPL antibodies in vivo may create a prothr ombotic state on ECs, which may be the first pathophysiological event of th rombosis in APS.