Key inflammatory pathways underlying vascular remodeling in pulmonary hypertension.

Independent of the underlying cause, pulmonary hypertension (PH) remains a devastating condition that is characterized by limited survival. Cumulating evidence indicates that in addition to a dysbalance of mediators regulating vascular tone and growth factors promoting vascular remodeling, failure to resolve inflammation and altered immune processes play a pivotal 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, T cells, dendritic cells, and mast cells. Dysfunctional bone morphogenic protein receptor 2 (BMPR2) signaling and dysregulated immunity enable the accumulation of macrophages and other inflammatory cells in obliterative vascular lesions. Regulatory T cells (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.

[Pathobiology, pathology and genetics of pulmonary hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Pathobiologie, Pathologie und Genetik der pulmonalen Hypertonie: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (PH) are also valid for Germany. While the guidelines contain detailed recommendations regarding clinical aspects of pulmonary arterial hypertension (PAH) and other forms of PH, they contain only a relatively short paragraph on novel findings on the pathobiology, pathology, and genetics. However, these are of great importance for our understanding of this complex disease both from a clinical and scientific point of view, and they are essential for the development of novel treatment strategies. To this end, a number of current data are relevant, prompting a detailed commentary to the guidelines, and the consideration of new scientific data. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the pathobiology, pathology and genetics of PH. This article summarizes the results and recommendations of this working group.