Purpose of review: HDL and their main apolipoprotein (apo) constituent apoA-I are antiatherogenic. This has been predominantly attributed to the ability of apoA-I/HDL to efflux cholesterol from macrophages within atherosclerotic plaques. It is now emerging that a number of the protective properties of HDL may be due to their effects on the endothelium.
Recent findings: In addition to their well characterized anti-inflammatory and antioxidant effects, apoA-I and HDL regulate several other key biological pathways known to preserve endothelial function and promote vascular repair. The ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, and the scavenger receptor B type 1 mediate multiple intracellular signaling pathways as well as the efflux of cholesterol and/or oxysterols in response to apoA-I/HDL. Although cholesterol efflux triggers a host of signaling events in endothelial cells, there is evidence that some of the beneficial actions of HDL may occur independently of efflux.
Summary: Current data suggest that in endothelial cells ABCA1 and ABCG1 mediate the activation of intracellular signaling pathways primarily through the efflux of cholesterol and oxysterols to apoA-I/HDL. Interaction between HDL and scavenger receptor B type 1 initiates the greatest number of known signaling pathways and there is evidence that some of these are activated independent of efflux.