Conclusions
It is widely accepted that oxLDL play a pivotal role in endothelial dysfunction and atheroma formation; the mechanisms involved are less clear. Recent research suggests that oxLDL may affect caveolae architecture and function in a complex interplay which leads to endothelial cell dysfunction. Caveolae are widely expressed on EC where they act as gatekeeper for LDL infiltration into the intima. Subendothelial accumulation and subsequent oxidation of LDL represent key events in atherogenesis. LDL transcytosis in EC occurs via caveolae, and SR-B1 and ALK1 are the main receptors involved. On the other hand, oxLDL are also present in the circulation from where they can be taken up at the EC interface by LOX-1 receptor, which induces the activation of many signaling pathways, leading to the establishment of a pro-inflammatory and pro-coagulant state in EC. Although SR-B1 has been recently demonstrated to be involved in oxLDL transcytosis, excluding a role for LOX-1, a crosstalk between caveolae and LOX-1 seems to exist. First, LOX-1 activity depends on an intact caveolae system. Second, its activity regulates the expression of the caveolar protein Cav-1 andvice versa . On the other hand, caveolae are important for signal transduction as they can concentrate and/or segregate not only receptors but also signalling intermediates. Their function is strictly correlated to their composition rich in cholesterol which allows a certain degree of plasticity. OxLDL and oxysterols have been reported to affect the content and/or the distribution of cholesterol into caveolae. Whether this event results in an aberrations of signalling cascades which are relevant for the development of atherosclerosis is expected but remains to be established.
Thus, even though multiple evidences point to an interplay between caveolae and oxLDL, as one of the mechanisms underlying oxLDL-induced EC dysfunction, some aspects remain contradictory and the information fragmentary. Future research is expected to further shed light on the connections between these players, focusing on the crosstalk between LDL receptor- and caveolae-mediated signalling and how this may be affected by changes in membrane cholesterol.