PLASMA ENDOTHELIN CORRELATES WITH ANTIENDOTHELIAL ANTIBODIES IN PATIENTS WITH MIXED CONNECTIVE-TISSUE DISEASE

Background Elevated circulating levels of the vasoactive peptide endot helin-1 have been reported in various cardiovascular disorders. Becaus e these conditions are frequently associated with endothelial dysfunct ion and damage and the vasoconstrictor effect of endothelin-1 is belie ved to be produced at the local vascular level, it is uncertain whethe r circulating endothelin-1 is a causal factor in enhanced vascular ton e or instead a marker of endothelial injury. Methods and Results We te sted whether elevated immunoreactive endothelin-1 could be detected by radioimmunoassay in plasma and whether endothelin-1 levels correlated with antiendothelial autoantibodies in patients with mixed connective tissue disease. Venous blood samples were collected from 21 patients in the morning after an overnight fast and before medication. The plas ma immunoreactive endothelin-1 level was 2.7+/-0.5 pg/mL (range, 1.1 t o 5.2 pg/ml; n=9) and 7.3+/-1.5 pg/mL (range, 2.8 to 20.7 pg/mL; n=12) in patients who had no antiendothelial antibodies and in patients wit h antiendothelial antibodies, respectively. These latter values were s ignificantly (P<.001) increased compared with 10 age-matched healthy v olunteers (2.0+/-0.3 pg/mL; range, 0.5 to 3.0 pg/mL). Plasma endotheli n-1 level strongly correlated with antiendothelial antibodies (r(s)=.8 36, n=21, P<.001), whereas there was no correlation between age, systo lic and diastolic blood pressures, antinuclear antibodies, and duratio n of the disease and endothelin-1 values. The incidence of Raynaud's p henomenon and angina did not differ significantly in patients with low and high endothelin-1 levels. Conclusions This study showed that mixe d connective tissue disease is associated with elevated plasma immunor eactive endothelin-1 and that endothelin-1 levels significantly correl ate with antiendothelial autoantibodies. These findings suggest that i ncreases in plasma endothelin-1 concentration may be secondary to vasc ular injury and do not necessarily represent enhanced susceptibility t o vasoconstriction.