Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary arterial pressures and right ventricular hypertrophy. While treatments to delay disease progression are available, PAH has a poor prognosis eventually leading to right heart failure and death.
PAH is characterized by constant remodeling of the pulmonary artery by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), fibroblasts (FBs) and endothelial cells (ECs). Such adverse remodeling eventually leads to increased pressure in the right ventricle with subsequent right ventricular hypertrophy and failure. Although inborn genetic variation plays an important role in PAH, several factors including drugs and environmental cues can significantly contribute to its pathogenesis. While much attention was drawn into investigating and developing therapies related to the most well understood signaling pathways in PAH, in the last decade, a shift towards understanding the gene-environment interaction driving the disease occurred. The Costantino lab investigates the transcriptional regulation, cell-cell interaction and phenotypic changes underpinning PAH development. These experimental and translational aims will be accomplished by state-of-the-art molecular biology, conditional mouse models and unique biobanks of PAH patients (Figure).
Figure. Translational approach to PAH