Modulation of lipid droplet biogenesis by p38 MAPK and caspase-1 in docosahexaenoic acid-induced EA.hy926 endothelial cell apoptosis

Abstract

Endothelial cells form a single layer of endothelium that lines the inner surface of the blood vessels. Healthy endothelial cells play important roles in the maintenance of the circulation homeostasis, while endothelial cell apoptosis has been implicated in the pathology of cardiovascular diseases. Lipid droplets (LDs) are multifunctional organelles that can be formed in endothelial cells during various fatty acid-induced apoptosis. However, the role of LDs in endothelial cell apoptosis and the mechanism of action have received limited attention. Our previous study showed that docosahexaenoic acid (DHA) induces endothelial cell apoptosis through the activation of mitogen-activated kinases (MAPKs) and caspases, and suggested a critical role of p38 MAPK and unknown caspases other than caspase-8, -9, and -3 in the modulation of apoptosis. Therefore, the current study is to investigate the regulatory mechanism of lipid droplet biogenesis by p38 MAPK and caspase-1 in DHA-induced EA.hy926 endothelial cell apoptosis. Our results showed that p38 MAPK and caspase-1 formed a positive feedback loop in upregulating LD biogenesis. Inhibiting the formation of LDs through diacylglycerol acyltransferases suppression but not caspase-1 inhibition led to an alleviation of cell apoptosis. Inhibition of LD biogenesis also negatively impacted the activation of p38 MAPK and caspase-1. Our study suggested a role of the interaction between p38 MAPK and caspase-1 in the modulation of LD biogenesis and apoptosis in DHA-treated endothelial cells, and revealed a potential role of LD in the modulation of the signal transduction involving p38 MAPK and caspase-1.