Key inflammatory pathways underlying vascular remodeling in pulmonary hypertension

Independent of the underlying cause, pulmonary hypertension (PH) remains adevastating condition that is characterized by limited survival. Cumulating evidence indicates that in addition to adysbalance of mediators regulating vascular tone and growth factors promoting vascular remodeling, failure to resolve inflammation and altered immune processes play apivotal role in the development and progression of PH. Here, we highlight the role of key inflammatory pathways in the pathobiology of vascular remodeling and PH, and discuss potential therapeutic interventions that may halt disease progression or even reverse pulmonary vascular remodeling. Perivascular inflammation is present in all forms of PH, and inflammatory pathways involve numerous mediators and cell types including macrophages, neutrophils, Tcells, dendritic cells, and mast cells. Dysfunctional bone morphogenic protein receptor2 (BMPR2) signaling and dysregulated immunity enable the accumulation of macrophages and other inflammatory cells in obliterative vascular lesions. Regulatory Tcells (Tregs) were shown to be of particular relevance in the control of inflammatory responses. Key cytokines/chemokines include interleukin-6, functioning via classic or trans-signaling, macrophage migratory inhibitory factor (MIF), but also other mediators such as neutrophil-derived myeloperoxidase. The expanding knowledge on this topic has resulted in multiple opportunities for sophisticated therapeutic interventions