Endothelial dysfunction, a major event in atherosclerosis: PPIs impair endothelial function through activation of PAI-1

Abstract

Aim: Endothelial dysfunction is a major risk factor for cardiovascular disease(CVD) and atherosclerosis. Proton pump inhibitors(PPIs) like Esomeprazole(Nexium) are widely used drugs for the treatment of gastroesophageal reflux disease. Recently, our laboratory discovered that PPIs inhibit a key enzyme dimethylarginine dimethylaminohydrolase(DDAH), which may lead to endothelial dysfunction. In addition, our clinical databases indicate that PPI use is associated with cardiovascular risk. We believe that PPIs pose a major risk for CVD by impairing endothelial function. The aim of my project is to investigate the mechanistic basis by which PPIs increase endothelial dysfunction that may lead to development of CVDs including atherosclerosis.