Figure 5.

Schematic representation of HA metabolism in SMCs loaded with oxidized LDL (oxLDL). Nontoxic concentrations of oxLDL are driven inside the SMCs by the upregulation of the scavenger receptor LOX-1. Accumulation of oxLDL leads to ER stress with overexpression of the UPR factors CHOP and GRP78 as well as activation of the LXR sterol sensor system. One or both systems induce the overexpression in the nucleus of several genes: LOX-1, HAS2, and HAS3. The HASs are active on the plasma membrane where they synthesize HA that interacts with CD44 present on immune cells, driving their adhesion, which contributes to the inflammatory status of the atherosclerotic lesion.