A review on thromboangiitis obliterans pathophysiology: thrombosis and angiitis, which is to blame?

A century has passed since thromboangiitis obliterans (TAO), or Buerger's disease, was first described, but the etiology remains unclear. It is still uncertain as to whether thrombosis or vascular inflammation is the first event. TAO is an episodic inflammatory and thrombotic-occlusive vascular disease of unknown origin. The involvement of the distal vessels and nerves within the neuro-vascular bundles occurs almost always in legs and occasionally in arms. The cumulative data demonstrate that at the cellular and molecular levels, at least four main components of inflammatory reactions, including endothelial cells, platelets, leukocytes and sensory neurons, might be involved in TAO pathogenesis. The interactions among these cells in an altered microenvironment of small- and medium-sized vessels may also orchestrate the onset of TAO events. In this review, the factors that may promote thrombosis and angiitis are reconsidered at three levels: (1) host characteristics such as male gender and genetic background; (2) probable triggers including cigarette smoking and infectious agents; and (3) environmental factors such as chronic anxiety and mental stress as a consequence of low socioeconomic status. At each level, the interactions among vascular endothelium, platelets, leukocytes and sensory neurons are discussed.