Caveolin-1 (Cav-1) is the major structural protein essential to the formation of the caveolae in endothelial cells. Cav-1 is thought to play an important role in the regulation of cellular cholesterol homeostasis, a process that needs to be properly controlled to limit and prevent cholesterol accumulation and eventually atherosclerosis. Genetic ablation of Cav-1 on an apoE knockout background inhibits the progression of atherosclerosis, while re-expression of Cav-1 in the endothelium promotes lesion expansion by affecting several processes including endothelial cell proliferation, migration, and nitric oxide production in vitro and increased expression of vascular cell adhesion molecule-1. Specifically, in vivo study shows that loss of Cav-1 reduces LDL infiltration into the artery wall and inhibits progression of atherosclerosis. However, surprisingly, we found that knock down of Cav-1 in human endothelial cells increases the binding and uptake of diI-LDL in vitro suggesting that Cav-1 decreases transcytosis of LDL. Moreover, Caveolin-1 has also been implicated in the regulation of inflammation in endothelial cells. Here we show that Cav-1 affects the induction of cell adhesion molecules in endothelial cells by inflammatory mediators including TLR2 ligand Pam3cys, IL-1B, and TNF. Specifically, knock-down of Cav-1 in human endothelial cells decreases the induction of ICAM-1, VCAM-1 and SELE in both mRNA and protein levels. Furthermore, we also show that silencing of Cav-1 attenuates the major signaling pathways that are involved in the induction of cell adhesion molecules including MAPK, AKT, JNK-AP1 and NF-κB pathways.
NF-κB, but not p38 MAP Kinase, is required for TNF-α-induced expression of cell adhesion molecules in endothelial cells