The Status of Nitric Oxide and its Backup, Heme Oxygenase 1, in Thromboangiitis Obliterans

Background: Until recently, a gene polymorphism in the promoter region of endothelial nitric oxide synthase has been suggested as a risk factor for thromboangiitis obliterans (TAO) development. The aim of this study was to compare the metabolites of nitric oxide (NO) and its backup, heme-oxygenase-1 (HMOX1), between TAO patients and those of a smoking control group matched by race, age, sex, and smoking habits. Methods: Twenty-four male Caucasian TAO patients and 20 male Caucasian controls enrolled in the study. Their smoking habits were matched based on the serum cotinine levels of 17 of the TAO patients and the 20 controls. A colorimetric kit was used to measure NO, and an enzyme-linked immunosorbent assay kit was used to measure cotinine and HMOX1 levels. Results: The mean serum level of NO metabolites in the TAO group was significantly less than in the controls (p = 0.03) and also significantly less in the patients with below-knee amputations than in non-amputees (p= 0.018). Also, HMOX1 was significantly greater in the TAO patients than in the controls (p= 0.01). No significant correlation was found between NO and HMOX1 (p = 0.054). Conclusions: Nitric oxide may play a pivotal role in TAO development and its outcome. However, the intact HMOX1 pathway may demonstrate the unique role of NO, which cannot be compensated for by HMOX1 and whose absence may make patients susceptible to developing TAO. In addition, another pathway besides NO, with influence on vascular tone and hemostasis, might be involved in TAO development, such as the autonomic nervous system. Further studies are suggested regarding these issues.