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Onset of peripheral arterial disease: role of endothelin in endothelial dysfunction.

OBJECTIVES
Endothelial dysfunction and inflammation are understood to contribute to the onset of peripheral arterial disease (PAD), and endothelin (ET) may play an important role in this process. This study investigated the role of ET in PAD, and its relationships with symptoms, endothelial dysfunction and inflammation.


METHODS AND RESULTS
This cross-sectional study enrolled 141 participants: 66 patients with PAD and intermittent claudication, 37 patients with PAD and critical ischemia, and 38 healthy controls aged under 35 years. There were no gender distribution differences between control and diseased groups. Moreover, no differences were observed in age or cardiovascular risk factors distribution between patients with critical ischemia and patients with claudication. Plasma ET concentrations were significantly higher in patients vs. controls (8.76+/-77.1 vs. 6.45+/-0.89 pmol/l, respectively; P=0.002). Nevertheless, patients with claudication exhibited significantly higher plasma ET concentrations vs. patients with critical ischemia (10.97+/-7.9 vs. 4.82+/-2.57 pmol/l, respectively; P<0.001). Otherwise, significantly greater serum concentrations of C-reactive protein (CRP) were observed in patients with critical ischemia vs. patients with claudication (16.94 vs. 4.73 mg/l, respectively; P=0.001) and controls (0.96 mg/l; P=0.001). Plasma concentrations of ET had a modest negative correlation with serum concentrations of CRP (-0.165; P=0.095).


CONCLUSION
Plasma concentrations of ET in patients with PAD are greatest in early disease; ET concentrations decrease substantially and inflammation arises as disease advances. Serum CRP concentrations exhibit a modest negative correlation with those of ET.