Para-bile-osis Establishes a Role for Nonbiliary Macrophage to Feces Reverse Cholesterol Transport.

Elimination of excess cholesterol by the reverse cholesterol transport (RCT) pathway opposes atherosclerotic cardiovascular disease. RCT begins with the mobilization of excess free cholesterol from macrophage foam cells in the artery wall to high-density lipoproteins. After esterification of cholesterol in the plasma compartment by lecithin cholesterol:acyltransferase, cholesteryl esters can be selectively delivered to the liver via the class B type 1 scavenger receptor. Alternatively, CETP (cholesterol ester transfer protein) may exchange cholesteryl esters for triglycerides on apolipoprotein B–containing lipoproteins, which can deliver cholesterol to hepatocytes by receptor-mediated endocytosis. Cholesterol elimination from the liver requires transport across the canalicular surface by the ABCG5/G8 transporter or the BSEP (bile salt export protein, ABCB11) after cholesterol conversion to primary bile acids. However, a fraction of cholesterol is reabsorbed in the proximal small intestine via NPC1L1 (Niemann-Pick C1-Like 1) and bile acids in the distal small intestine through the combined actions of the apical sodium-dependent bile acid transporter and intestinal bile acid transporter, thereby limiting neutral and acidic sterol loss from the body.