Nantes Université, CHU Nantes*, CNRS, INSERM, l'institut du thorax, F-44000, Nantes, France.
L'institut du thorax, INSERM, CNRS, UNIV NANTES, BP 70721, 8 Quai Moncousu, 44007, Nantes cedex 1, France.
Curr Atheroscler Rep. 2022 Mar;24(3):153-160. doi: 10.1007/s11883-022-00995-y. Epub 2022 Feb 9.
The transintestinal cholesterol efflux (TICE) pathway is the second described route for plasma cholesterol fecal elimination. This article summarizes recent TICE research progresses, involving TICE inducers, molecular determinants of this pathway, and its role in lipoprotein metabolism.
TICE is an active pathway in mice, rats, and humans. Kinetic measurements showed that under basal conditions, the relative contribution of TICE in fecal elimination of plasma cholesterol is quantitatively less important than the hepatobiliary pathway. However, the amplitude of TICE can be induced by numerous nutritional factors and pharmacological drugs. More importantly, by contrast with the stimulation of biliary cholesterol excretion that is associated with an increased risk of gallstone formation, TICE appears as a safer therapeutical target. Finally, several independent studies have demonstrated that TICE is actively contributing to the anti-atherogenic reverse cholesterol pathway reinforcing the interest to better understand its mode of action. The discovery of TICE and the understanding of its mode of action open new therapeutical perspectives for patients at high risk of cardiovascular diseases.
肠肝胆固醇外排(TICE)途径是第二种描述的血浆胆固醇粪便消除途径。本文总结了 TICE 的最新研究进展,包括 TICE 诱导剂、该途径的分子决定因素及其在脂蛋白代谢中的作用。
TICE 在小鼠、大鼠和人类中是一种活跃的途径。动力学测量表明,在基础条件下,TICE 在血浆胆固醇粪便消除中的相对贡献在定量上不如肝胆途径重要。然而,许多营养因素和药物可以诱导 TICE。更重要的是,与胆汁胆固醇排泄的刺激相比,胆汁胆固醇排泄增加了胆结石形成的风险,而 TICE 似乎是一个更安全的治疗靶点。最后,几项独立的研究表明,TICE 积极参与抗动脉粥样硬化的胆固醇逆向转运,这增强了人们对其作用机制的兴趣。TICE 的发现及其作用机制的理解为心血管疾病高危患者开辟了新的治疗前景。