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.