Vascular Remodeling in Hypoxia-induced Pulmonary Hypertension: Role of Cytokines and MicroRNAs

Abstract

Vascular remodeling is the most important factor in the pathogenesis of pulmonary hypertension and is mainly driven by changes in the expression of the bone morphogenetic protein receptor type II (BMPR2) that controls the growth of pulmonary arterial endothelial cells and vascular smooth muscle cells. Mutations in the BMPR2 are identified in about 70% of familial and in up to one third of idiopathic pulmonary arterial hypertension. Reduced expression of BMPR2 however have also been identified in non-genetic forms of the disease, for example in hypoxia-induced pulmonary hypertension. This dysregulation might be due to the action of microRNAs (miRs), which are small RNA fragments that bind the complementary mRNA of BMPR2 and result in posttranscriptional gene silencing. Here, we review the most important pathways identified in the context of miRs and hypoxia-induced pulmonary hypertension and emphasize the potential of miRs as targets for future causative therapies.