EVIDENCE OF ELEVATED PLASMA THROMBOMODULIN IN ATHEROSCLEROSIS

Thrombomodulin (TM) is a very efficient natural anti-thrombin glycopro tein expressed on the endothelial cell surface. Circulating soluble th rombomodulin is also detected by enzyme imunoassay in plasma and repre sents some fragments of membrane TM with various molecular weight. Pla sma TM (TMp) levels are elevated in diseases associated with endotheli um damage. We have explored TMp in patients with atheromatous disease and compared its level with others endothelial cell markers, particula rly those who indicate cell activation, as tissue-type plasminogen act ivator (t-PA), inhibitor of plasminogen activator (PAI-1) and prostacy clin (PG12). Thirty seven patients with documented atheromatous artery disease were included in this study. They were not diabetics and thei r hepatic and renal functions were normal. Mean age was 71 +/- years. Routine serum parameters were checked out as well as others more speci fic for endothelium activation (TMp, PG12, PAI-1, t-PA) measured by en zyme immunoassay. Patients were classified according to three localiza tions of atheromatous involvement : 15 patients with peripheral occlus ive arteriopathy disease (POAD) - 6 with coronary artery disease (CAD) ; and 16 with polyvascular involvement (POLY). They were compared wit h 21 controls without any vascular lesions (mean age : 43 +/- 1 3 year s). In controls TMp was 36 +/- 8 ng/ml without significant change acco rding with age and sex. In patients whatever the localization of ather oma, TMp was found significantly higher : POAD = 51.3 +/- 19.7 ng/ml ( p = 0.003) ; CAD = 49.2 +/- 15.4 ng/ml (p 0.008) ; POLY = 49.6 +/- 17. 2 ng/ml (p = 0.003). A positive correlation was pointed out in all pat ients between TMp and t-PA (p = 0.047), TMp and PG12 (p = 0.008). A po sitive correlation between TMp and t-PA (p = 0.034) was found only in the subgroup with POAD. In this study, there was no correlation betwee n TMp and the following parameters : leucocytes, haemoglobin, choleste rol, HDL, LDL-cholesterol, Lp(a), fibrinogen. We conclude that in pati ents with atheromatous artery involvement, TMp levels were elevated wi th a trend (non clearly demonstrated here) of a positive correlation b etween TMp and the extend of vascular disease. TMp is considered yet a s a marker of endothelial injury. A positive correlation with other ac tivation endothelial cell markers was found. Further studies will be n ecessary to understand the mechanisms of endothelial soluble TM libera tion in atheroma, and to test the hypothesis is according to which sol uble TM is a natural anticoagulant (J Mal Vasc, 1993, 18, pages 112-11 8).