Bile acids are primarily produced in the liver and secreted into the intestine to aid in the digestion and absorption of dietary fats. However, bile acids have also been shown to have effects on the cardiovascular system, including the heart. Bile acids have been found to increase heart rate and contractility in animal studies. In addition, they can activate specific receptors in the heart, such as the TGR5 receptor, which has been linked to increased cardiac contractility, reduced cardiac fibrosis, and improved cardiac function in some studies¹. Another proposed mechanism by which bile acids may affect the heart is through their interaction with nuclear receptors, such as the farnesoid X receptor (FXR) and the pregnane X receptor (PXR), which are expressed in cardiac tissue. Activation of these receptors by bile acids has been shown to have both beneficial and detrimental effects on the heart. On one hand, activation of FXR by bile acids has been shown to have a cardioprotective effect by reducing inflammation and oxidative stress in the heart. FXR activation has also been shown to improve glucose and lipid metabolism, which can help reduce the risk of developing cardiovascular disease. Interestingly, ursodeoxycholic acid is a hydrophilic BA, and it is used as a therapeutic drug to reverse harmful cardiac effects caused by hydrophobic elevated BAs². Excessive levels of bile acids can lead to a condition known as bile acid cardiotoxicity, characterized by impaired heart function. The exact mechanisms underlying bile acid cardiotoxicity are not fully understood, but it is thought to be related to oxidative stress, inflammation, and alterations in calcium signalling pathways in the heart³. This project aims to elucidate pathways involved.
