Biliary and nonbiliary contributions to reverse cholesterol transport

Area of Science:

• Cardiovascular Science
• Metabolic Regulation
• Gastroenterology

Background:

• Reverse cholesterol transport (RCT) is essential for eliminating excess cholesterol.
• Traditionally, RCT was thought to rely solely on biliary secretion.
• Recent findings reveal a persistent RCT in biliary insufficiency, highlighting a nonbiliary pathway.

Purpose of the Study:

• To review the relative contribution of biliary and nonbiliary RCT components.
• To explore the therapeutic potential of targeting the intestine for cholesterol excretion.
• To discuss the role of the small intestine in cholesterol homeostasis and atherosclerotic cardiovascular disease (ASCVD) treatment.

Main Methods:

• Review of existing literature on RCT pathways.
• Analysis of studies investigating genetic and surgical models of biliary insufficiency.
• Examination of research on transintestinal cholesterol efflux (TICE) and its regulation.

Main Results:

• The proximal small intestine facilitates cholesterol secretion via transintestinal cholesterol efflux (TICE).
• While quantitatively less significant than the biliary route, TICE is highly inducible.
• Intestine-specific activation of RCT demonstrates protective effects against ASCVD in preclinical models.

Conclusions:

• The small intestine is a critical regulator of cholesterol balance, controlling both absorption and TICE.
• Targeting intestinal cholesterol regulation presents a promising therapeutic strategy for ASCVD.
• Integrated regulation of cholesterol absorption and TICE in the intestine offers new avenues for managing cholesterol and preventing cardiovascular disease.