Selective cyclooxygenase-2 inhibition reduces endothelial dysfunction and improves inflammatory status in patients with intermittent claudication.
OBJECTIVE
Both endothelial dysfunction and a proinflammatory state are present during the early stages of atherosclerosis. In this context, increased expression of cyclooxygenase-2 (COX-2) results in higher levels of vasoconstrictive and proinflammatory substances. The aim of this study was to investigate the influence of COX-2 activity on endothelial dysfunction associated with peripheral arterial disease (PAD).


METHODS
Brachial artery flow-mediated dilatation (BAFMD), endothelin and high-sensitivity C-reactive protein (hsCRP) levels, and the lipid profile were assessed in 40 patients with intermittent claudication. Of these, 20 were randomly assigned to a group in which they received the selective COX-2 inhibitor celecoxib for 1 week (Group 1), while the other 20 served as controls (Group 2).


RESULTS
In Group 1, BAFMD increased significantly both 3 hours after the first dose of celecoxib (3.33+/-4.11 vs. 6.97+/-3.27%; P=.008) and 1 week after (3.33+/-4.11 vs. 7.09+/-4.40%; P=.001). The endothelin level decreased significantly in Group 1 (2.92+/-1.87 vs. 1.93+/-1.07 pg/ ml; P=.018), as did the levels of hsCRP (4.78+/-2.73 vs. 2.95+/-2.11 mg/l; P=.023) and low-density lipoprotein cholesterol (106.38+/-18.89 vs. 90.8+/-28.58 mg/dl; P=.019). In Group 2, none of these parameters changed significantly.


CONCLUSIONS
COX-2 products contribute to endothelial dysfunction and an inflammatory state in PAD. This study's findings provide evidence that these phenomena are implicated in the initiation of atherosclerosis and could prove a new means of investigating alternative approaches to the treatment of early-stage disease.
Flórez
Aurora
A
Servicio de Angiología y Cirugía Vascular. Hospital Universitario de Getafe. Getafe. Madrid. España. aurora.florez@terra.es
de Haro
Joaquín
J
Martínez
Esther
E
Varela
César
C
Bleda
Silvia
S
Acín
Francisco
F
D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D007383:Intermittent Claudication / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib