Recent advances and future trends in regulating transintestinal cholesterol excretion: Potential for nano-based therapeutic strategies

Cardiovascular disease (CVD)-related mortality continues to increase, imposing persistently high social and economic burdens. Accumulating evidences have indicated that plasma cholesterol concentration is closely related to the morbidity and prognosis of CVD. The balance of cholesterol metabolism has profound implication for preventing and decreasing CVD. Therefore, it is necessary to clarify the pathways and mechanisms of cholesterol metabolism in the human body. Both hepatobiliary pathway and transintestinal cholesterol excretion (TICE) pathway could clean out cholesterol through feces, but the treatment of cholesterol-lowering by targeting hepatobiliary pathway is not satisfactory, and aiming at the TICE pathway may be a more effective strategy. However, the specific mechanism of TICE remains largely unknown. Herein, this review summarizes the past and present understanding of TICE development history, put a special emphasis on the process and molecular mechanisms as well as the influence factor of TICE. Additionally, this article also predicts and discusses the potential mechanisms of candidate genes and non-coding RNAs that may mediate TICE. Furthermore, we discuss the emerging potential of nanocarrier-based delivery systems for targeted modulation of TICE, offering new possibilities for cholesterol-lowering therapies. This review may provide new strategies for promoting cholesterol elimination from body and reducing CVD risk, and provide a theoretical basis for the future development of TICE-targeted drugs.