Implication of miR-204/RUNX2-dependent calcification pathway in pulmonary arterial hypertension (1089.23)

Introduction: Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized by occurrence of several vascular lesions. Interestingly, some biological pathways implicated in these lesions are also implicated in calcification processes. Nonetheless, the role for calcification lesions in PAH has never been explored. miR-204, which is downregulated in PAH, is implicated in calcification processes by directly regulating the pro-calcification transcription factor RUNX2. RUNX2 also regulates cell proliferation by activating HIF-1. Thus, we hypothesized that miR-204 downregulation in PAH triggers RUNX2 expression promoting calcification and vascular lesions in PAH. Methods and results: Using human explanted lungs, fresh distal pulmonary arteries (PAs) and freshly isolated pulmonary artery smooth muscle cells (PASMC) from both control and PAH patients, we demonstrated a significant downregulation of miR-204 and an upregulation of RUNX2 in PAH compared to controls. The increase in RUNX2 in PA...