Patients with antiphospholipid syndrome display endothelial perturbation.
BACKGROUND
There is strong evidence that antiphospholipid antibodies (aPL) perturb endothelium both in vitro and in experimental animal models. by inducing a vasculopathy and an endothelial pro-inflammatory/coagulant phenotype. However, few contrasting studies raised the issue about the possibility to detect a comparable endothelial perturbation in anti-phospholipid syndrome (APS) patients. The aim of this observational case-control study was to evaluate several parameters of endothelial perturbation in patients with APS and without any other atherosclerosis risk factor.


METHODS
We investigated plasma levels of soluble adhesion molecules (s-ICAM-1, s-VCAM-1, s-E-selectin), soluble thrombomodulin (sTM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) by solid-phase assays in 40 selected APS patients and 40 age- and sex-matched healthy subjects. In addition, we evaluated circulating endothelial cells by flow cytometry and brachial artery flow-mediated vasodilation. Patients and controls were free of conditions known to affect both the biological and the functional endothelial parameters.


RESULTS
Plasma levels of sTM, s-E-selectin and s-VCAM-1 did not differ from controls, while a significant increase in s-ICAM-1 (P = 0.029), t-PA (P = 0.003) and vWF titres (P = 0.002) was found. Circulating mature endothelial cells were also significantly higher in patients than in controls (P = 0.05) and decreased during both vitamin K antagonists (P = 0.001) and antiplatelet (P = 0.032) treatments. Mean brachial artery flow-mediated vasodilation responses were significantly impaired compared to healthy subjects (P = 0.0001).


CONCLUSIONS
As a whole these findings indicate that APS patients display an endothelial perturbation in the absence of other detectable traditional risk factors for atherosclerosis.
Cugno
Massimo
M
Department of Internal Medicine, University of Milan, IRCCS Foundation Maggiore Hospital Policlinico, Mangiagalli, Regina Elena, Italy.
Borghi
Maria Orietta
MO
Lonati
Laura Maria
LM
Ghiadoni
Lorenzo
L
Gerosa
Maria
M
Grossi
Claudia
C
De Angelis
Valentina
V
Magnaghi
Gaia
G
Tincani
Angela
A
Mari
Daniela
D
Riboldi
Piersandro
P
Meroni
Pier Luigi
PL
D000328:Adult; D000368:Aged; D017152:Antibodies, Antiphospholipid / Q000276:immunology / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis; D001916:Brachial Artery / Q000502:physiology*; D002339:Carotid Arteries / Q000473:pathology*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004108:Dilatation, Pathologic; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
D017152:Antibodies, Antiphospholipid; D015815:Cell Adhesion Molecules; D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator