Risk Factors, Mechanisms and Treatments of Thromboangiitis Obliterans: An Overview of Recent Research

Abstract

Background:: Thromboangiitis obliterans (TAO) is a nonatherosclerotic thrombotic-occlusive vasculitis that affects the vessels of the small and medium sized extremities. No explicit etiology or pathogenesis of TAO has been proven, and more effective treatments are needed. Objective: : To summarize and present an overview of recent advances regarding the risk factors, mechanisms and treatments of TAO and to organize the related information into figures to provide a comparatively complete reference. Methods:: We searched PubMed for English-language literature about TAO without article type limits, including articles about the risk factors, pathological mechanisms and treatments of TAO in the last 10 years with essential supplements (references over ranges and English abstracts of Russian literature). Results:: After screening content of literatures, 99 references were evaluated. We found that risk factors of TAO include smoking, gene factors and periodontal diseases. The underlying mechanism of TAO involves in oxidative stress, immunity, hemodynamic changes, inflammation and so on. Moreover, similarities in genetic factors and cigarette relevance existed between periodontal diseases and TAO, so further relationship study of them are required. For TAO treatment, medicine, endovascular intervention and revascularization surgery, autologous cell therapy and novel therapies were also mentioned. Besides, a hypothesis that infection triggers autoimmunity in TAO could be speculated, in which TLR4 plays a key role. Conclusions:: 1. Puts forward a hypothesis that infections can trigger autoimmunity in TAO development, in which TLR4, as a key role, can activate immune signaling pathways and induce autoimmune cytokines expression. 2. Suggests a reconsideration about the association between periodontal diseases and TAO, such as they just share the same high-risk population. Controlling periodontal disease severity in TAO studies may provide new clues. 3. For TAO treatment, endovascular intervention and autologous cell therapy both showed promising long-term therapeutic effectiveness, in which autologous cell therapy is becoming more popular, although more clinical comparisons needed.

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

“…Despite the studies on pathophysiology (reviewed in [29,51], actually, the detailed etiopathogenesis and molecular mechanisms are still unknown. Among the possible biomolecular hypotheses [10,12,14,18,[20][21][22][23]27,50,[54][55][56], oxidative stress has been crucially indicated as an important factor for both the initiation and progression of WBD [30,31,51,54].…”

“…Among the immunologic and inflammatory biomolecular hypotheses for the WBD disease, some biomarkers and biochemical mechanisms have been identified. Among them, 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]).…”

Autologous Peripheral Blood-derived Stem Cells Transplantation for Treatment of no-option Angiitis-induced Critical Limb Ischemia: 10-year Management Experience

“…Although not as common as ASO-induced CLI, AICLI still represents an important subgroup of advanced PAD. Meanwhile, AICLI is characterized with higher incidence in East Asians, much lower onset age, and a higher proportion of No-option ones, which causes a tricky dilemma that conventional revascularization modalities hardly work in these patients with higher levels of expectation of limb salvage, especially in China where there is a large population of patients with AICLI [22,23]. This is one of the reasons why we select patients with NO-AICLI as our treatment subjects by SCT.…”

Autologous peripheral blood-derived stem cells transplantation for treatment of no-option angiitis-induced critical limb ischemia: 10-year management experience

“…Although not as common as ASO-induced CLI, AICLI still represents an important subgroup of advanced PAD. Meanwhile, AICLI is characterized with higher incidence in East Asians, much lower onset age, and a higher proportion of No-option ones, which causes a tricky dilemma that conventional revascularization modalities hardly work in these patients with higher levels of expectation of limb salvage, especially in China where there is a large population of patients with AICLI [22,23]. This is one of the reasons why we selected patients with NO-AICLI as our treatment subjects by SCT.…”