The Critical Effect of Bile Acids in Atherosclerosis

Atherosclerosis (AS) is one of the most common cardiovascular diseases and is the leading cause of arteriosclerotic cardiovascular disease. Bile acids are not only the products of cholesterol metabolism, but also an important class of signaling molecules. Bile acids exert their biological effects through the bile acid receptor signaling pathways. Bile acid receptors are widely distributed in human organs and tissues. The activation of transcriptional and signaling cascades controls bile acid metabolism and synthesis, lipid and carbohydrate metabolism, immune cell expression, and inflammatory responses. A large body of evidence indicates that bile acids play an important role in the initiation and development of AS, and are strongly associated with AS risk factors. The major bile acid receptors, nuclear receptor farnesoid X receptor (liver) and membrane receptor G protein-coupled receptor 5, exhibit anti-atherosclerotic effects. Other nuclear receptors exert different anti-atherosclerotic or pro-atherosclerotic effects. In this review, we summarize the current knowledge on the effects of bile acids and their receptors in AS and explore the pathway of bile acids involved in atherosclerotic lesions. The main research based on animal models or cell/tissue culture experiments is also discussed. This review provides new ideas for the development of novel therapeutic approaches for AS prevention and treatment.