The Role of Bile Acids in Cardiovascular Diseases: from Mechanisms to Clinical Implications

Abstract

Bile acids (BAs), key regulators in the metabolic network, are not only involved in lipid digestion and absorption but also serve as potential therapeutic targets for metabolic disorders. Studies have shown that cardiac dysfunction is associated with abnormal BA metabolic pathways. As ligands for several nuclear receptors and membrane receptors, BAs systematically regulate the homeostasis of metabolism and participate in cardiovascular diseases (CVDs), such as myocardial infarction, diabetic cardiomyopathy, atherosclerosis, arrhythmia, and heart failure. However, the molecular mechanism by which BAs trigger CVDs remains controversial. Therefore, the regulation of BA signal transduction by modulating the synthesis and composition of BAs is an interesting and novel direction for potential therapies for CVDs. Here, we mainly summarized the metabolism of BAs and their role in cardiomyocytes and noncardiomyocytes in CVDs. Moreover, we comprehensively discussed the clinical prospects of BAs in CVDs and analyzed the clinical diagnostic and application value of BAs. The latest development prospects of BAs in the field of new drug development are also prospected. We aimed to elucidate the underlying mechanism of BAs treatment in CVDs, and the relationship between BAs and CVDs may provide new avenues for the prevention and treatment of these diseases.

Impact of Mesotherapy with Sodium Deoxycholate on Liver: Metabolic- and Sex-Specific Insights in Swiss mice

“…In recent years, it has been discovered that bile acids such as DC can bind to multiple tissue receptors and act as metabolic regulators of pathways related to glucose, lipids, and amino acids metabolism, homeostasis maintenance, and gut microbiota, which explain their implication in several metabolic disorders [17, 20]. In the liver, DC binds to FXR, which regulates glycolipid metabolism and endothelial function, which are enrolled in cardiovascular disease risk [17]. In turn, FXR activation reduces circulating DC [36] because it acts as a bile acid sensor in the enterohepatic circulation, and it maintains bile acid homeostasis by modulating the expression of genes enrolled in bile acid synthesis, transport, and excretion [21].…”

“…In recent years, it has been discovered that bile acids such as DC can bind to multiple tissue receptors and act as metabolic regulators of pathways related to glucose, lipids, and amino acids metabolism, homeostasis maintenance, and gut microbiota, which explain their implication in several metabolic disorders [17, 20]. In the liver, DC binds to FXR, which regulates glycolipid metabolism and endothelial function, which are enrolled in cardiovascular disease risk [17].…”

“…Walker et al (2015) showed that DC 100 mg sc increases DC serum levels within the endogenous normal range, and after 12 hours, it returned to basal levels; thus, DC might have a systemic action through its receptors [9]. Moreover, DC binds to several tissues that express its receptors and may be implicated in a series of metabolic diseases [17, 20]. With this in mind, we hypothesize that the chronic use of DC in mesotherapy modulates the hepatic metabolism and gene expression through the farnesoid X receptor (FXR) [21].…”

Metabolomic signatures of carfilzomib‐related cardiotoxicity in patients with multiple myeloma

“…[26][27][28] Studies have associated abnormal bile acid metabolism disturbances with cardiac dysfunctions. 26,29 T-UDCA is a hydrophilic bile acid and is known to inhibit endoplasmic reticulum (ER) stress. 30 ER stress stimuli such as oxidative stress, ischemic insult, and altered calcium homeostasis can lead to cardiomyocyte apoptosis to HF.…”

“…24,25 Bile acids have long been recognized as key regulators in the metabolic network and are involved in lipid metabolisms. [26][27][28] Studies have associated abnormal bile acid metabolism disturbances with cardiac dysfunctions. 26,29 T-UDCA is a hydrophilic bile acid and is known to inhibit endoplasmic reticulum (ER) stress.…”