Plasma markers of endothelial dysfunction in pulmonary hypertension

Study objectives: To evaluate and to correlate endothelial cell dysfunction , using recently available plasma markers, with the magnitude of pulmonary artery pressure in patients with severe pulmonary hypertension (PH). Design: Selected plasma markers of endothelial cell dysfunction were studie d: nitric oxide (NO), thrombomodulin, tissue factor pathway inhibitor, and soluble endothelium, leukocyte, and platelet selectins (sE-, sL-, sP-select ins, respectively). Setting: Padova University Hospital and Department of Pathology and Pharmac ology, Loyola University of Chicago, Chicago, IL. Patients: Fifteen patients had severe PH (four men and 11 women; mean age, 49.7 +/- 2.9 years: seven patients had primary pulmonary hypertension [PPH] and eight patients had secondary pulmonary hypertension [SPH]), and 20 pat ients were healthy control subjects. Measurement and results: In patients with PH, sP- and sE-selectins were ele vated, whereas sL-selectin was lower in comparison with the selectin levels in control subjects. However, the differences between patients with PH and control subjects were significant only for sL-selectin (p < 0.0001) and sE -selectin (p < 0.03). The NO level was significantly lower in patients with PH compared with the NO level in control subjects (p < 0.01). No differenc e in tissue factor pathway inhibitor level was noted between control subjec ts and patients with PH. Only a weak correlation was found between thrombom odulin plasma levels and magnitude of systolic pulmonary artery pressure (r = -0.528, p < 0.05). Conclusions: Our data are in keeping with the evidence for significant endo thelial cell dysfunction in patients with PH and the need for chronic antic oagulation believed to increase survival in these patients. In addition, th ese data seem to suggest a need for newer agents that are able to increase the antithrombotic endothelial function.