Overview of bile acid signaling in the cardiovascular system

Table 1 Hydrophobicity of bile acid increases with the decrease of OH groups

Hydrophobicity	Types of bile acids
Low	UDCA
↓	CA
	CDCA
	DCA
High	LCA

CA: Cholic acid; CDCA: Chenodeoxycholic acid; DCA: Deoxycholic acid; LCA: Lithocholic acid; UDCA: Ursodeoxycholic acid.

Table 2 Central receptor involved in bile acid signaling

Receptor	Tissue	Cardiovascular tissue	Ligand	Regulatory mechanism	Direct action	Ref.
FXR	Liver, kidney, gastrointestinal	Arteries, cardiomyocytes	CDCA, LCA, DCA	Regulates BSEP expression and participates in the process of liver injury, activates I-BABP expression to mediate cholesterol secretion, inhibits vascular inflammation, decreases lipogenesis synthesis, increases lipoprotein clearance to prevent atherosclerosis, ameliorates post-MI cardiac dysfunction and remodeling	No	[14-16]
PXR,VDR	Liver	t-Tubulescardiomyocytes	LCA	Down-regulates CYP7A1 expression to eliminate BA toxicity, maintains lipid metabolism, regulates intracellular calcium flow and contractile forces, maintains the normal operation of cardiomyocytes	No	[17-19]
M	Nervous, intestinal, gastrointestinal	Aorta, cardiomyocytes	TC, LCT, TCA	Stimulates acetylcholine-induced inositol phosphorylation and MAP kinase phosphorylation, inhibits cAMP, amplitude, reduces CM contraction	Yes	[20,21]
S1P	Liver, nervous, immune	Endothelial smooth muscle, cardiomyocytes	TCA, UDCA	Inhibits formation of cAMP and antagonizes adrenergic receptor-mediated contractile force, protects heart from ischemia/reperfusion injury, involved in remodeling and differentiation of cardiac fibroblasts	No	[22,23]
TGR5	Liver, glands, fat, muscle, enteric, immune	Aortic endothelial	CA, DCA, CDCA, TLCA, TCDCA	Inhibits the secretion of TNF induced by LPS, downregulates GSK3 and upregulates PKB associated with cardiac hypertrophy, metabolic transformation of energy in cardiomyocytes	Yes	[24,25]
BK channel	Liver, brain	Endothelial, cardiomyocytes	LCA	Cause vasodilation in liver and cerebral artery, plays role in diabetes, through mitochondrial BK channels confer cardioprotection	Yes	[26-28]

BA: Bile acid; BK channel: Large conductance voltage- and Ca²⁺-activated potassium (K⁺) (BK) channels; BSEP: Bile salt export pump; CA: Cholic acid; cAMP: Cyclic AMP; CDCA: Chenodeoxycholic acid; CM: Myocardial cell; CYP7A1: Cholesterol 7α hydroxylase; DCA: Deoxycholic acid; FXR: Farnesoid X receptor; GSK3: Glycogen synthase kinase-3; I-BABP: Encoding intestinal bile acid binding protein; LCA: Lithocholic acid; LCT: Lithocholyltaurine; LPS: Lipopolysaccharide; M: Muscarinic; MAP: Mitogen-activated; MI: Myocardial infarction; PKB: Protein kinase B; PXR: Pregnane X receptor; RXR: Retinoic acid X receptor; S1P: Sphingosine-1-phosphate; TC: Taurocholate; TCA: Taurocholic acid; TCDCA: Taurodeoxycholic acid; TGR5: Takeda G-protein-coupled receptor 5; TLCA: Taurolithocholic acid; TNF: Tumor necrosis factor; UDCA: Ursodeoxycholic acid; VDR: Vitamin D receptor.