Nanoparticles in Medicine: A Focus on Vascular Oxidative Stress

Figure 4

Chronic activation of the renin-angiotensin system (RAS) contributes to oxidative stress and vascular dysfunction. Increased levels of angiotensin II (AT II) lead to endothelial dysfunction through AT II receptor 1 (AT1R) activation, which in turn induces vascular oxidative stress by increasing NADPH oxidase (Nox) activity and xanthine oxidase (XO) expression. Both enzymes produce superoxide anion (O₂⁻), which scavenges nitric oxide (NO) by forming peroxynitrite (ONOO⁻), consequently decreasing NO bioavailability and causing endothelial dysfunction. Moreover, AT II can undermine the induction of the antioxidant system thioredoxin (TRX), enhancing levels of H₂O₂ and contributing to vascular oxidative stress. H₂O₂ is the most stable and abundant ROS which, as a signalling messenger, maintains physiologic vascular homeostasis, but its overproduction is related to vascular dysfunction. In contrast, AT II receptor 2 (AT2R) activation can counteract the lesser NO bioavailability induced by vascular oxidative stress via eNOS phosphorylation, thereby increasing its activity.