Increased vein wall thickness in Behçet's disease: from intravascular mechanical stress to vascular remodelling and venous thrombosis.

Behçet’s disease (BD) is a chronic, multisystem inflammatory disorder characterized by recurrent oral ulcers, genital ulcers, and uveitis, together with various manifestations. Vascular involvement occurs in 25–30% of BD patients. Recent studies on BD have remarkably claimed that even Behçet patients without vascular problems exhibit increased vein wall thickness (VWT). Researchers suggested that this increase in VWT may have a diagnostic value for BD. However, the mechanisms responsible for this process and its clinical significance remain unclear. In this Perspective article, we describe how aberrant responses to mechanical stress, such as intravascular pressure, can lead to venous wall remodeling and increased VWT. Specifically, we will discuss the process from vascular remodeling to thrombosis, examining the roles of Piezo1 mechanotransducers, activated adventitial cells, and secreted angiogenic factors and cytokines. In this process, the possible role of innate immunity and adaptive immune activation will be discussed in the context of the pathogenesis of MHC-I-opathy group diseases. According to our hypothesis, the activation of fibroblasts and other immune cells in the adventitia primarily initiates an adventitial inflammation. Cytokines and angiogenic factors produced from macrophages and fibroblasts during this inflammatory process lead to proliferation in vasa vasorum (VV) alongside a fibroinflammatory response. In this phase, which can be explained as a remodeling phase, VWT increases. When the vasa vasorum that are fragile and unable to form collateral are inflamed, damage and ischemia develop in the vascular wall. These events disrupt endothelial integrity and lead to deep venous thrombosis (DVT). Understanding these changes can aid in the development of preventative strategies to mitigate the onset of DVT in BD patients.