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
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.