Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic role for endothelin 1
T Atsumi, MA Khamashta, RS Haworth… - … : Official Journal of …, 1998 - Wiley Online Library
T Atsumi, MA Khamashta, RS Haworth, G Brooks, O Amengual, K Ichikawa, T Koike…
Arthritis & Rheumatism: Official Journal of the American College …, 1998•Wiley Online LibraryObjective 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 …
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 …
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‐β2‐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.
Conclusion
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.
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