The Imbalance among Oxidative Biomarkers and Antioxidant Defense Systems in Thromboangiitis Obliterans (Winiwarter-Buerger Disease).

Hiva Sharebiani,Ferdinando Mannello,Bahare Fazeli,Daniela Ligi,Rosanna Maniscalco

doi:10.3390/jcm9041036

Abstract

(1) Background: Thromboangiitis obliterans or Winiwarter-Buerger disease (WBD), is an inflammatory, thrombotic occlusive, peripheral vascular disease, usually occurring in young smokers. The pathophysiological mechanisms underlying the disease are not clearly understood. The aim of this study is to investigate the imbalance between oxidants and antioxidants occurring in these patients. (2) Patients and Methods: In this cross-sectional study, 22 male patients with WBD and 20 healthy male smoking habit matched control group were included. To evaluate the possible sources of oxidative stress, the antioxidant biomarkers, and the markers of lipid peroxidation and protein oxidation, serum samples were analyzed for total oxidative status (TOS), total antioxidant capacity (TAC), myeloperoxidase (MPO), coenzyme Q10 (CoQ10), superoxide dismutase (SOD), glutathione reductase (GR), malondialdehyde (MDA), and protein carbonyl (PC) activity and/or content. (3) Results: The circulating levels of TOS, TAC, and CoQ10 were significantly higher in WBD patients, with respect to healthy smokers as controls. No significant difference was found among the serum level of PC, total cholesterol, MPO, and GR activity in WBD patients and healthy smoker controls. The activity of SOD and the mean serum level of MDA were significantly lower in WBD patients, with respect to healthy smoker controls. (4) Conclusion: Considerably high levels of oxidative stress were detected in WBD patients, which were greater than the antioxidant capacity. The low level of MDA may be associated with the enzymatic degradation of lipid peroxidation products. High levels of CoQ10 and low levels of SOD may be related to a harmful oxidative cooperation, leading to the vasoconstriction of WBD, representing a promising tool to discern possible different clinical risks of this poorly understood peripheral occlusive disease.

Highlights

To evaluate the possible sources of oxidative stress, the antioxidant biomarkers, and the markers of lipid peroxidation and protein oxidation, serum samples were analyzed for total oxidative status (TOS), total antioxidant capacity (TAC), myeloperoxidase (MPO), coenzyme Q10 (CoQ10), superoxide dismutase (SOD), glutathione reductase (GR), malondialdehyde (MDA), and protein carbonyl (PC) activity and/or content
(4) Conclusion: Considerably high levels of oxidative stress were detected in Winiwarter-Buerger disease (WBD) patients, which were greater than the antioxidant capacity
Since the milestone landmark articles [1,2], thromboangiitis obliterans or Winiwarter-Buerger disease (WBD) has been defined as an inflammatory, thrombotic, occlusive, peripheral vascular disease, which usually occurs in young male smokers

Summary

Introduction

Since the milestone landmark articles [1,2], thromboangiitis obliterans or Winiwarter-Buerger disease (WBD) has been defined as an inflammatory, thrombotic, occlusive, peripheral vascular disease, which usually occurs in young male smokers. A significant relationship between smoking (both tobacco and cannabis products) and progression of WBD has been identified [5], smoking per se cannot explain the prevalence and distribution of this harmful vascular disease [6]. Despite efforts in previous years and advances in medical therapy [4,7,8], WBD patients may benefit only by blocking smoking habits (abstinence of all tobacco/cannabis product use) and through targeted endovascular therapy, effective for preserving limb loss/amputation, and useful for accelerating the healing process in Buerger’s ischemic ulcers [9]. Among the immunologic and inflammatory biomolecular hypotheses for the WBD disease, some biomarkers and biochemical mechanisms have been identified. Crucial roles are played by cytokines and chemokines [10,11,12], adhesion molecules [13,14,15], Rickettsia rickettsii and Porphyromonas gingivalis (through toll-like receptors) [16,17,18,19], angiogenic factors [20], catecholamines [21], inflammation on sympathetic ganglia [22], T cells/macrophages/dendritic cells (intima infiltration of vessels) [23], accumulation of immunoglobulins, immune complexes and complement factors on sub-endothelial elastic lamina [24], urinary cotinine [25], circulating auto-antibodies [26], heme oxygenase 1 and the inducible isozyme of nitric oxide synthase [27], and matrix metalloproteinases [28] (as reviewed in [29])

Objectives

Methods

Results