Laurens F Reeskamp1, Emma C E Meessen2, Albert K Groen3,4. 1. Department of Vascular Medicine. 2. Department of Endocrinology and Metabolism. 3. Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam. 4. Department of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands.
Abstract
PURPOSE OF REVIEW: To discuss recent insights into the measurement and cellular basis of transintestinal cholesterol excretion (TICE) in humans and to explore TICE as a therapeutic target for increasing reverse cholesterol transport. RECENT FINDINGS: TICE is the net effect of cholesterol excretion by the enterocyte into the intestinal lumen and is the balance between input and output fluxes through the enterocytes. These fluxes are: cholesterol excretion into the intestinal lumen mainly via ATP-binding cassette (ABC) G5/8, cholesterol absorption from the intestine by Niemann-Pick C1 like protein 1, the uptake of plasma lipoproteins by enterocytes at the basolateral membrane, and the excretion of cholesterol in chylomicrons into the lymph. Multiple studies have shown that TICE contributes to fecal neutral sterol (FNS) excretion in humans. TICE can be targeted with plant sterols, liver X receptor agonists, bile acids, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors. SUMMARY: TICE contributes significantly to FNS excretion in humans, independently of the biliary pathway. Knowledge about its underlying cellular mechanisms surges through in-vivo and in-vitro studies in mice and humans. TICE might be an interesting therapeutic target for increasing cholesterol disposal with the feces. Albeit multiple therapeutic options are available, studies showing clinical benefit are still needed.
PURPOSE OF REVIEW: To discuss recent insights into the measurement and cellular basis of transintestinal cholesterol excretion (TICE) in humans and to explore TICE as a therapeutic target for increasing reverse cholesterol transport. RECENT FINDINGS: TICE is the net effect of cholesterol excretion by the enterocyte into the intestinal lumen and is the balance between input and output fluxes through the enterocytes. These fluxes are: cholesterol excretion into the intestinal lumen mainly via ATP-binding cassette (ABC) G5/8, cholesterol absorption from the intestine by Niemann-Pick C1 like protein 1, the uptake of plasma lipoproteins by enterocytes at the basolateral membrane, and the excretion of cholesterol in chylomicrons into the lymph. Multiple studies have shown that TICE contributes to fecal neutral sterol (FNS) excretion in humans. TICE can be targeted with plant sterols, liver X receptor agonists, bile acids, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors. SUMMARY: TICE contributes significantly to FNS excretion in humans, independently of the biliary pathway. Knowledge about its underlying cellular mechanisms surges through in-vivo and in-vitro studies in mice and humans. TICE might be an interesting therapeutic target for increasing cholesterol disposal with the feces. Albeit multiple therapeutic options are available, studies showing clinical benefit are still needed.
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