D108 CELL FATE DECISIONS: SENESCENCE, REPAIR, AND REGENERATION: Targeting The Phospholipase A2 Receptor (pla2r1) And Its Downstream Effectors To Inhibit Lung Cell Senescence In Chronic Obstructive Pulmonary Disease (COPD)

Objectives: To demonstrate that PLA2R1 is a major player in the development of cell senescence and COPD and to develop and validate innovative tools to inhibit PLA2R1 and its downstream targets in preclinical models Methods and Results: Compared to control lungs, lungs from patients with COPD had higher PLA2R1 protein levels, and their vessels exhibited prominent PLA2R1 immunostaining. PLA2R1 mRNA and protein levels in were also higher in the cultured pulmonary-artery smooth muscle cells (PA-SMCs) and pulmonary endothelial cells (P-ECs) from patients' lungs, which exhibited early-onset cell senescence manifesting as fewer population doublings (PDLs) and as an increase in beta-galactose-positive cells.