There has been a lot of discussion recently about high-density lipoprotein (HDL) cholesterol and how the physiologic functioning of HDL might relate to cardiovascular disease (CVD) risk. Since it is the excess cholesterol that accumulates in macrophages embedded in the arterial wall that eventually leads to an increase in risk of CVD events, the principal function of HDL cholesterol that affects this increase in risk is its ability to promote efflux of cholesterol from macrophages. How this occurs and how this is measured in humans is the subject of this presentation.
The concept of “cholesterol efflux capacity” as a biomarker of HDL function in humans has been around for several years. It has been well demonstrated in controlled settings in vitro that HDL cholesterol promotes removal, or efflux, of cholesterol from cells such as macrophages, but clearly humans in vivo differ in their CVD risk and it is logical to assume that there are interindividual differences among humans in how functionally competent their HDL cholesterol is at promoting the efflux of cholesterol from their macrophages. The question is, how do we actually go about testing the idea that people differ in the ability of their HDL cholesterol to promote efflux, and how do we demonstrate that this is relevant to cardiovascular risk?
This Figure represents a schematic of HDL metabolism and the pathways by which it promotes cholesterol efflux from macrophages. The arrows in the Figure represent the transport of cholesterol. On the right-hand side of the Figure cholesterol is effluxed from macrophages into a nascent, lipid-poor form of HDL, known as pre-beta HDL, or apoA-I with a little bit of lipid, via a pathway mediated by an active transporter known as ABCA1. A second transporter, ABCG1, also transports cholesterol out of macrophages, but this efflux is into more mature HDL particles that have a lot of cholesterol ester and are larger and more buoyant.
J Clin Lipidol. 2011; 5(6).