Arterial disease and thrombosis in the antiphospholipid syndrome: a pathogenic role for endothelin 1

Arthritis Rheum. 1998 May;41(5):800-7. doi: 10.1002/1529-0131(199805)41:5<800::AID-ART5>3.0.CO;2-J.


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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Anticardiolipin / pharmacology
  • Antibodies, Monoclonal
  • Antiphospholipid Syndrome / blood
  • Antiphospholipid Syndrome / complications*
  • Arterial Occlusive Diseases / blood
  • Arterial Occlusive Diseases / etiology*
  • Cells, Cultured
  • DNA Primers / chemistry
  • Endothelin-1 / blood*
  • Endothelins / biosynthesis
  • Endothelins / genetics
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycoproteins / immunology
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Protein Precursors / biosynthesis
  • Protein Precursors / genetics
  • RNA, Messenger / biosynthesis
  • Thrombosis / blood
  • Thrombosis / etiology*
  • beta 2-Glycoprotein I


  • Antibodies, Anticardiolipin
  • Antibodies, Monoclonal
  • DNA Primers
  • Endothelin-1
  • Endothelins
  • Glycoproteins
  • Protein Precursors
  • RNA, Messenger
  • beta 2-Glycoprotein I