Heart and bile acids – Clinical consequences of altered bile acid metabolism

Abstract

Cardiac dysfunction has an increased prevalence in diseases complicated by liver cirrhosis such as primary biliary cholangitis and primary sclerosing cholangitis. This observation has led to research into the association between abnormalities in bile acid metabolism and cardiac pathology. Approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy. Bile acids are directly implicated in this, causing QT interval prolongation, cardiac hypertrophy, cardiomyocyte apoptosis and abnormal haemodynamics of the heart. Elevated maternal serum bile acids in intrahepatic cholestasis of pregnancy, a disorder which causes an impaired feto-maternal bile acid gradient, have been associated with fatal fetal arrhythmias. The hydrophobicity of individual bile acids in the serum bile acid pool is of relevance, with relatively lipophilic bile acids having a more harmful effect on the heart. Ursodeoxycholic acid can reverse or protect against these detrimental cardiac effects of elevated bile acids.

Pediatric cirrhotic cardiomyopathy: Impact on liver transplant outcomes

“…It seems that other factors may contribute to the QTc time prolongation. Vasavan et al described elevated bile acids as a factor and ursodeoxycholic acid as a reliable treatment (prophylactic and therapeutic). This is in line with the fact that we found significantly higher levels of serum‐bilirubin in our patients with pathological (>450 ms) QTc intervals.…”

“…That we could not find this association for bile acids may be founded on a bias due to ursodeoxycholic acid treatment. Since this treatment could be prophylactic, it would be of interest to know if patients in studies with high amounts of pathological QTc and cirrhosis were also treated with ursodeoxycholic acid as in our study. In summary, it has to be taken into account that a prolonged QTc interval could be a phenomenon that is associated with liver disease but not directly related to the stage of liver fibrosis.…”

Mechanisms of Interactions between Bile Acids and Plant Compounds—A Review

“…Changes in the bile acid pool are linked to cardiac dysfunctions, liver diseases, biliary stones development, and diabetes. Inflammation, apoptosis, and cell death may be caused by cytotoxicity induced by microbial changes of bile acid structures [17,24,122,123]. Hydrophobicity is an important determinant of the cytotoxicity of bile acids [124].…”

Overview of Bile Acids Signaling and Perspective on the Signal of Ursodeoxycholic Acid, the Most Hydrophilic Bile Acid, in the Heart

“…A summary of the findings from these two studies is given in Figure 2. Increased hydrophobic BAs have been associated with cardiac hypertrophy, CMs apoptosis, and abnormal cardiac hemodynamics [111]. Recently, a clinical study reported that the total bile acid level is associated with the enlargement of left atrial volume and interferes with the hyperdynamic circulation in patients with cirrhosis [112].…”

“…Recently, a clinical study reported that the total bile acid level is associated with the enlargement of left atrial volume and interferes with the hyperdynamic circulation in patients with cirrhosis [112]. Hydrophobic BAs have been shown to increase the risk of atherosclerosis development and other CVDs through the inhibition of endoplasmic reticulum stress, which interrupts lipogenic pathways, free cholesterol-induced cell death in macrophages [113], reduction of major histocompatibility complex (MHC)-associated antigen presentation [114], and diminishing of the inflammatory environment [111]. In contrast, the hydrophilic BA UDCA was shown to exert anti atherogenic activity in diabetic atherosclerosis mouse model through reduction of endoplasmic reticulum stress, receptor for advanced glycation endproduct (RAGE) signaling, and proinflammatory responses, including ROS production and Nf-κB activation [106].…”