RT Journal Article SR Electronic T1 LSC Abstract – Histone deacetylase 7 mediated metabolic remodeling: A new crosslink between pulmonary hypertension and cancer JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP PA5105 DO 10.1183/13993003.congress-2016.PA5105 VO 48 IS suppl 60 A1 Elisabetta Gamen A1 Prakash Chelladurai A1 Friedrich Grimminger A1 Rajkumar Savai A1 Werner Seeger A1 Soni Savai Pullamsetti YR 2016 UL http://erj.ersjournals.com/content/48/suppl_60/PA5105.abstract AB Pulmonary arterial smooth muscle cells (PASMCs) from Pulmonary Hypertension (PH) patients and several PH animal models are characterized by suppressed mitochondria-dependent apoptosis and hyperpolarization. Similarly to lung cancer (LC) cells, PH-PASMCs have reduced glucose oxidation and increased cytoplasmic glycolysis. Protein acetylation and its enzymes such as histone deacetylases (HDACs) may play a role in the control of metabolism.We assessed the regulation of Class IIa HDACs (HDAC4, 5, 7 and 9) in human and experimental models of PH and lung cancer. By using primary culture of healthy (control-PASMCs), idiopathic derived PASMCs (IPAH-PASMCs) and human non-small cell lung cancer cells (A549), we aim to identify the role of HDAC7 in the apoptosis-associated metabolic and mitochondrial remodeling.We observed that among class IIa HDACs, HDAC7 is the only commonly upregulated in human and experimental models of PH and LC. Immunohistochemistry revealed HDAC7 upregulation in the medial layer of the pulmonary vasculature in PH and in cancer cells. This finding could be reproduced using ex vivo exposure of control-PASMCs to hypoxia and appeared to be independent from HIF1-α regulation. Similar upregulation was observed in several lung cancer cell lines. Pharmacological inhibition and genetic ablation of HDAC7 by siRNA causes cell apoptosis and decreased mitochondrial polarization and pyruvate/lactate production. Interestingly, specific potassium channels and metabolic enzymes associated with glycolytic shift are regulated by HDAC7.Our data demonstrate that HDAC7 drives various hallmarks such as apoptosis, mitochondrial and metabolic deregulation of PH and lung cancer.This abstract has been presented previously at the European Respiratory Society's Lung Science Conference in March 2016.