Increased reactive oxygen species (ROS) levels induce alteration of the vascular structures and functions through inflammation, cell proliferation and migration, apoptosis, and extracellular matrix alteration.1–3 Several experimental evidences support the presence of an oxidative stress component in hypertension and atherosclerotic diseases. Indeed, a tight connection between oxidative stress and endothelial disfunction has been observed in hypertensive subjects.4–8 The major players in ROS-related alteration are NO (nitrogen monoxide) bioavailability, ONOO– (peroxynitrite ions), eNOS (endothelial Nitric Oxide Synthetase), and oxidized LDL (Ox-LDL). NO is the most important endothelial relaxing factor with potent anti-atherosclerotic properties, therefore, all the conditions causing a reduction of the NO levels lead to the initiation or acceleration of atherosclerotic processes (Figure 1).4–6,9 NO quickly reacts with ROS to generate ONOO– , which affects eNOS functioning,4,7 leading to NOS uncoupling.7,10
Figure 1. Mechanisms underlying endothelial dysfunction and the functional consequences of decreased vascular bioavailability of nitric oxide (NO). The picture was retrieved from reference number 11.
In this context, uncoupled eNOS contributes to the increase of ROS levels and LDL can be oxidized to Ox-LDL, corroborating the development and progression of atherosclerosis.8,9,12,13 Ox-LDLs can be internalized into endothelial cells triggering signaling pathways promoting foam cell formation, the development of fatty streaks8,9,12,13 and the up-regulation of ACE, which induces blood pressure alterations. As a matter of fact, it has been hypothesized that ox-LDL play a crucial role in the connection between dyslipidemia and hypertension.8,9,12–15 Hence, experimental evidences clearly support that ROS-mediated oxidative stress induces deleterious effects by triggering a cascade of signals that results into endothelial disfunction promoting the progression of cardiovascular, atherosclerosis and metabolic disorders, both in human and animal models.5,8,9,16–18
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