The Structure and Function of Serum Opacity Factor: A Unique Streptococcal Virulence Determinant That Targets High-Density Lipoproteins

Figure 10

Reverse cholesterol transfer pathway (RCT). RCT is the major pathway for transfer of excess cholesterol (C) from peripheral tissues to the liver for disposal as bile. High levels of cholesterol can be toxic and the accumulation of cholesterol (C) in macrophages lining the blood vessels transforms these cells to foam cells leading to the development of plaque and atherosclerosis. Cholesterol is removed from these tissues and transferred to HDL by interactions with ATP binding cassette receptors ABCA1, ABCG1/4, and SR-B1 or by diffusion. The interaction between ABCA1 and apo A-I is the dominant pathway for removal of excess cholesterol from macrophages followed by an interaction between HDL and ABCG1. Together these two receptors account for about 70% of the efflux of excess cholesterol [86]. The size of HDL is modulated as its load of cholesterol increases and by interactions with various plasma factors such as lecithin cholesterol acyltransferase (LCAT) [87]. Free cholesterol removed from these tissues is esterified by LCAT and subsequently removed by liver cells by interactions with HDL. SOF enhances this process in several ways [88]. First, it releases free apo A-I, which is a better acceptor of free cholesterol than HDL. Secondly, it forms neo-HDL, a particle that is similar to pre-β HDL, which is also a better acceptor of cholesterol than HDL. Thirdly, SOF enhances cholesterol esterification, which may allow a more efficient uptake of cholesterol by the liver.