Abstract 15944: ALDH1A3 Regulates Chromatin Remodeling and Smooth Muscle Proliferative Genes in PAH

Pulmonary arterial hypertension (PAH) is a life-threatening disease that is not effectively cured by current therapies. It is characterized by progressive occlusion of the vascular lumen owing to the abnormal growth of pulmonary artery smooth muscle cells (PASMC) occupying the neointima. The hyperproliferative PASMC phenotype is related to altered cell metabolism and gene expression, but how the two are connected is incompletely understood. RNAseq analyses of PASMC from 12 PAH vs. 9 control subjects identified heightened expression of aldehyde dehydrogenase 1 family, member A3 (ALDH1A3) among total 87 significantly changed genes (FDR<0.1). We hypothesized that ALDH1A3 could regulate proliferation through acetyl-CoA mediated changes in histone acetylation of pro-proliferative genes in PAH PASMC. Western immunoblots (WB) confirmed increased ALDH1A3 and H3K27ac in PAH vs. control PASMC (n=3, p<0.05). Reducing ALDH1A3 by RNAi decreased the proliferation of PASMC (MTT assay, n=3, p<0.05), and the expression of...