If we now move from HDL cholesterol levels and particle number to the concept of HDL functionality, we can ask: what is the most important, well-established function of HDL? It is to mobilize cholesterol from peripheral tissues and maintain a healthy cholesterol homeostasis. This model of reverse cholesterol transport (Figure) was promulgated by Glomset in 1964.[50] In this model, Glomset assumed that cholesterol was free-flowing from the macrophage, that it was bidirectional flow, and that through the LCAT reaction, cholesterol is trapped in the bloodstream, but that formation of cholesterol ester would prevent the back diffusion of cholesterol.
In this theory the greater the activity of LCAT, the greater the ability of HDL particles to carry the cholesterol in the bloodstream, and when the HDL particles became mature, cholesterol-enriched, spheroid particles, they can then interact with the liver. In other words, the function of the HDL particles is to take up cholesterol from the periphery and carry it to the liver to be disposed of into the bile and feces.
Glomset’s model of reverse cholesterol transport that has been in the lexicon for so many years; however, we know that the situation may not necessarily be relevant for humans because what we are concerned about is not the amount of cholesterol in the feces. What we are concerned about is the ability to get cholesterol out of the macrophages in the arterial walls, because when those macrophages are metabolically active and actively acquiring cholesterol, they can inflame the vessel wall by releasing inflammatory mediators, which can degrade the fibrous cap of the plaques and predispose the atherosclerotic lesions to rupture.
J Clin Lipidol. 2011; 5(6).[50]Glomset JA, Wright JL. Some properties of a cholesterol esterifying enzyme in human plasma, Biochim. Biophys. Acta 89 (1964), pp. 266–276.
