Targeting Early Atherosclerosis: A Focus on Oxidative Stress and Inflammation

Figure 3

Effects of oxLDL and oxidative stress on endothelium. LOX-1 activation by oxLDL induces endothelial oxidative stress by increasing NADPH oxidase (Nox) activity and uncoupling eNOS. Oxidative stress activates NF-κB through p38 mitogen-activated protein kinase (p38MAPK) and phosphatidylinositol 3-kinase (PI3K) transduction pathways initiating intranuclear apoptotic signal transduction. The formation of peroxynitrite (ONOO⁻) reduces nitric oxide (NO) and prostacyclin (PGI2) bioavailability leading to endothelial dysfunction. In addition, oxidative stress reduces PPARγ activity and adiponectin levels. Both of them stimulate AMP-activated protein kinase (AMPK) which in turn upregulates eNOS activity through Akt phosphorylation (Akt-P). Moreover, AMPK is a negative regulator of Nox.