Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic role for endothelin 1.
OBJECTIVE
To explore a possible correlation between endothelin 1 (ET-1), the most potent endothelium-derived contracting factor that modulates vascular smooth muscle tone, and arterial disease in patients with the antiphospholipid syndrome (APS).


METHODS
Plasma levels of ET-1 were measured in APS patients with (n = 16) and without (n = 11) arterial thrombosis and in non-APS patients with arterial thrombosis (n = 9). In addition, steady-state prepro-ET-1 messenger RNA (mRNA) levels were determined in endothelial cells treated with a range of human monoclonal anticardiolipin antibodies (aCL) (as anti-beta2-glycoprotein I antibodies) by semiquantitative 32P-dCTP-labeled reverse transcription-polymerase chain reaction.


RESULTS
Compared with healthy controls, markedly increased plasma levels of ET-1 were found in APS patients with arterial thrombosis (2.00 +/- 0.87 versus 0.96 +/- 0.37 pg/ml; P = 0.0001) but not in other groups. Three human monoclonal aCL induced prepro-ET-1 mRNA levels significantly more than did control monoclonal antibody lacking aCL activity.


CONCLUSIONS
Plasma ET-1 levels correlated significantly with a history of arterial thrombosis in patients with APS. Prepro-ET-1 mRNA was induced by human monoclonal aCL in the in vitro experimental system. The induction of ET-1 by antiphospholipid antibodies might contribute to increased arterial tone, leading to vasospasm and, ultimately, to arterial occlusion.
Atsumi
T
T
The Rayne Institute, St. Thomas' Hospital, London, UK.
Khamashta
M A
MA
Haworth
R S
RS
Brooks
G
G
Amengual
O
O
Ichikawa
K
K
Koike
T
T
Hughes
G R
GR
D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000150:complications*; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000209:etiology*; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D019332:Endothelin-1 / Q000097:blood*; D016232:Endothelins / Q000096:biosynthesis / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013927:Thrombosis / Q000097:blood / Q000209:etiology*; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D017931:DNA Primers; D019332:Endothelin-1; D016232:Endothelins; D006023:Glycoproteins; D011498:Protein Precursors; D012333:RNA, Messenger; D053482:beta 2-Glycoprotein I