Different Cytokine Patterns in BMPR2-Mutation-Positive Patients and Patients With Pulmonary Arterial Hypertension Without Mutations and Their Influence on Survival.

Abstract

Pulmonary arterial hypertension (PAH) covers a range of life-limiting illnesses characterized by increased mean pulmonary arterial pressures, which if untreated, lead to right heart failure and death. This is due to remodeling of the small-to-medium sized pulmonary vessels, which obstruct blood flow. Pulmonary arterial hypertension can be further categorized into idiopathic PAH (without any identifiable cause, 6th World Symposium class 1.11) and heritable PAH , (defined by mutations in specific genes, 6th World Symposium class 1.21), the most common affecting bone morphogenetic protein receptor type II (BMPRII)2 3. It is known that BMPR2-mutation positive patients have worse cardiac indices at presentation and a worse overall outcome compared to PAH without mutations4. Possessing a BMPR2 mutation also creates a pro-inflammatory state, through loss of endothelial barrier function5 and loss of antioxidant capability6. This then begs the question as to whether the mutation-positive groups have different underlying pathogenetic mechanisms and require different biomarkers and treatments, analogous to how EGFR-mutation positive non-small cell lung cancer patients respond to tyrosine kinase inhibition while the majority of NSCLC patients do not.