Ali Aliee - Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran & Student Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Farnaz Zahedi Avval - Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran & Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Hossein Taheri - General Surgery Department, Farabi Hospital, Kowsar Blvd, Mashhad, Iran.
Saeedeh Mehraban Moghadam - Inflammation and Inflammatory Diseases Division of Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Mohammad Soukhtanloo - Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Daryoush Hamidi Alamdari - Surgical Oncology Research Center, Emam Reza Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Bahare Fazeli - Inflammation and Inflammatory Diseases Division of Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran & VAS, European Independent Foundation in Angiology/Vascular Medicine. Milan, Italy.

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-۱ (HMOX۱), 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 ۲۰ male Caucasian controls enrolled in the study. Their smoking habits were matched based on the serum cotinine levels of ۱۷ of the TAO patients and the ۲۰ controls. A colorimetric kit was used to measure NO, and an enzyme-linked immunosorbent assay kit was used to measure cotinine and HMOX۱ levels. Results: The mean serum level of NO metabolites in the TAO group was significantly less than in the controls (p = ۰.۰۳) and also significantly less in the patients with below-knee amputations than in non-amputees (p= ۰.۰۱۸). Also, HMOX۱ was significantly greater in the TAO patients than in the controls (p= ۰.۰۱). No significant correlation was found between NO and HMOX۱ (p = ۰.۰۵۴). Conclusions: Nitric oxide may play a pivotal role in TAO development and its outcome. However, the intact HMOX۱ pathway may demonstrate the unique role of NO, which cannot be compensated for by HMOX۱ 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.

Cotinine, Heme oxygenase ۱, Nitric oxide, Peripheral arterial disease, Smoking, Thromboangiitis obliterans