CIRCULATING ENDOTHELIN-1 LEVELS IN SYSTEMIC-SCLEROSIS SUBSETS - A MARKER OF FIBROSIS OR VASCULAR DYSFUNCTION

Objective. To investigate the circulating levels of endothelin-1 (ET-1 ) in serum (sET-1) in patients with pulmonary disease [pulmonary fibro sis (PF) and pulmonary hypertension (PHT)], and renal involvement [hyp ertensive renal crisis (HRC)] in the 2 major subsets of systemic scler osis (SSc) in order to determine the significance of sET-1 levels in r elation to specific organ involvement or to the underlying pathogenic mechanisms of vascular damage and fibrosis. Methods. In addition to th e measurement of ET-1 in serum using a competitive radioimmunoassay, t he circulating levels of angiotensin converting enzyme (ACE) and plasm a von Willebrand factor (vWF) were measured as markers of endothelial damage in the various disease groups. Results. Levels of sET-1 were si gnificantly increased in 64 patients with diffuse systemic sclerosis ( dSSc) and 17 patients with primary Raynaud's phenomenon (RP) compared with 22 healthy individuals. sET-1 levels were equally elevated in dif fuse cutaneous disease (dcSSc) with only fibrotic dermal or lung patho logy compared with patients with additional PHT or HRC crisis. These o bservations were in marked contrast to the sET-1 levels seen in patien ts with the limited cutaneous form of SSc (lcSSc) where only patients with lcSSc with hypertensive lung or renal disease had significantly h igher levels of sET-1 than comparable lcSSc patients with only fibroti c dermal and lung disease. sET-1 levels were additionally found to cor relate with plasma vWF, skin fibrosis (skin score) and duration of dis ease in patients with SSc. Conclusion. The presence of significantly r aised sET-1 levels in patients with dcSSC with widespread fibrosis and patients with lcSSc with hypertensive disease and the relationship se en between sET-1 levels and markers of fibrosis and vascular damage su ggest that ET-1 may be important in the pathogenesis of both the fibro tic and vascular manifestations in SSc.