Arachidonic Acid Derivatives Prevent Serum Deprivation Induced Apoptosis of Pulmonary Artery Smooth Muscle Cells by Activating ProSurvival Pathway

Abstract

Pulmonary arterial hypertension is a debilitating disease, withprogressive remodelling of the pulmonary vessels. The remodelling becomesirreversible even after surgical correction of the cardiac defect. Patients withsevere PAH are predisposed to heart failure. Still, no permanent therapeuticalconsideration exist for this multifactorial disease. The strategical vascularremodelling is known to involve all the changes including Pulmonary ArterialSmooth Muscle Cell (PASMCs) proliferation and apoptosis. Emergingevidence show that several arachidonic acid metabolites are frequentlyinvolved in modulating pulmonary arteries. Arachidonic acid cytochromeP450 (CYP) metabolites 20- hydroxyeicosatetraenoic acid (20-HETE) and LOmetabolites 15-oxo-Eicosatetraenoic acid (15-oxo-ETE) are known to havepulmonary arterial functional and structural contributions. The effect of15-oxo-ETE and 20-HETE, and their contribution on the pathway ormechanism of inhibition of PASMCs apoptosis has not yet been revealed.This work was carried out to test the hypothesis if 20-HETE and 15-oxo-ETEhave the ability to protect the PASMCs from apoptosis. Our results revealedthe cellular mechanism of 20-HETE and 15-oxo-ETE, which served as a prosurvivalfactor to protect serum deprivation induced PASMCs againstapoptosis. This also identified that such an effect possibly is mediated viastimulation of Akt pathway. 20-HETE and 15-oxo-ETE protect the PASMCs,prolonging the viability by the two lipids in serum deprivation-inducedapoptosis of PASMCs. newline