Caveolin-1 and Atherosclerosis: Regulation of LDLs Fate in Endothelial Cells

Figure 1. Caveolin-1 and LDL trafficking: a schematic representation of different fates of LDLs after Cav-1-mediated trafficking. Receptors for LDL and oxLDL are localized in caveolae. Their interaction with Cav-1 favors uptake and transcytosis of LDL and oxLDL. When LDL are internalized through LDLR (green lines), they are degraded and cholesterol and LDLR are recycled in the plasma membrane. However, when LDLR interacts with PCSK9, the complex LDL-LDLR is internalized through Cav-1 (red lines), and the LDLR is degraded. Expression of Cav-1 is strictly related to internalization and transcytosis of LDLs. The overload of LDLs, as well the imbalanced activity of eNOS and iNOS, induces LDL oxidation and decreases their degradation leading to increased oxidative stress and attenuation of autophagy, thus contributing to endothelial dysfunction. These events, in turn, activate production and release of inflammatory factors contributing to the establishment of an inflammatory environment and to the recruitment of macrophages, thus favoring the onset and progression of atherosclerosis.