Research ArticlePulmonary Arterial Hypertension

NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary arterial hypertension

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Science Translational Medicine  13 Jun 2018:
Vol. 10, Issue 445, eaap7294
DOI: 10.1126/scitranslmed.aap7294

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In silico sleuthing for pulmonary hypertension

Cell proliferation and fibrosis (the accumulation of excess connective tissue) cause arterioles to thicken during pulmonary arterial hypertension (PAH). Aldosterone, a hormone involved in reactive oxygen species generation, wound healing, and fibrosis, is also increased in PAH. Samokhin et al. used in silico analysis to identify NEDD9 as a critical protein involved in vascular remodeling, fibrosis, and pulmonary hypertension. Oxidative modification of NEDD9 impaired its degradation and promoted collagen production. Mice lacking NEDD9 were protected from pulmonary hypertension, and collagen deposition, vascular remodeling, and cardiopulmonary metrics were normalized in a rat model of PAH treated with siRNA targeting NEDD9. This work suggests that therapeutic targeting of NEDD9 may be effective for combating vascular fibrosis in PAH.