Platelets and cytokines in concert with endothelial activation in patients with peripheral arterial occlusive disease

We tested the hypothesis whether circulating oncostatin-M (OSM), a cytokine that in vitro promotes fibrinogen biosynthesis and smooth muscle cell proliferation, or soluble CD40 ligand (CD40L; CD154), a leukocyte and platelet surface marker that stimulates endothelial cells, were associated: (a) with fibrinogen and other soluble cell adhesion molecules, such as P-selectin, vascular fell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 and platelet-endothelial cell adhesion molecule-1; or (b) with restenosis and platelet activation in 71 patients with peripheral arterial occlusive disease undergoing peripheral angioplasty (PTA). Platelet membrane activation markers (CD62P, CD63, activated GPIIb/IIIa) were immunologically measured at 0, 1, 24 and 48 h, and 3 and 6 months after PTA. Soluble cell adhesion molecules, endothelial markers and various hemostatic variables were measured before PTA. Of the patients, 42.3% developed restenosis within 6 months, defined as a > 50% reduction of the lumen at the site of balloon dilatation. Soluble CD40L was not higher in the restenosis group. Interestingly, patients with high CD40L showed significantly higher soluble VCAM-1 (P < 0.01) and thrombomodulin (P < 0.01), as well as trends for higher soluble P- and E-selectin. Platelet activation was found uniformly increased mostly at 1 and 24 h, as well as at 3 and 6 months. OSM was measurable in 53.5% (6.9 +/- 9.4 pg/ml) of the patients and undetectable in the others. No differences in the rate of restenosis was found in these two groups, which did not differ with respect to fibrinogen (3.14 +/- 1.00 versus 3.21 +/- 0.70 g/l), or the other parameters. In conclusion, soluble CD40L is associated with higher endothelial biological markers that might implicate its involvement in endothelial activation. Platelet activation, probably intermittent, might play a significant role through the expression of CD40L as a source of activation signals to the endothelial cells. Free circulating OSM does not seem to correlate directly with fibrinogen or with other acute phase reaction proteins, the synthesis of which it could influence in vitro, This might well not mean, however, that OSM lacks this activity in vivo. Blood Coag Fibrinol 11:165-173 (C) 2000 Lippincott Williams & Wilkins.