Bile Acid Signaling and Cardioprotection

Bile acids (BA) are classically known as an agent important in lipid absorption and cholesterol metabolism. Nowadays, BAs have been found to be involved in various cellular signaling pathways such as protein kinase cascades, cyclic AMP (cAMP) synthesis and calcium mobilization. In addition, they have also been shown to regulate glucose and energy homeostasis. Bile acids are ligands for several nuclear hormone receptors, including FXR. Recently, muscarinic receptor and TGR5, G-protein-coupled receptor (GPCR), have been suggested to play a role in bile acid activity which is independent of nuclear hormone receptors. Moreover, BAs have also been studied in other GPCR associated pathways, namely sphingosine-1-posphate and glucagon receptor. Hydrophobic bile acids have been proven to affect heart rate and its contraction. Elevated bile acids are associated with arrhythmias in adults and fetal heart. Altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase of serum bile acid concentrations. In contrast, the most hydrophilic BA known as ursodeoxycholic acid has been found beneficial in improving peripheral blood flow in chronic heart failure patients and protecting heart against reperfusion injury.