title: Bile acids regulate cardiovascular function.
abstract: Research over the last decade has uncovered roles for bile acids (BAs) that extend beyond their traditional functions in regulating lipid digestion and cholesterol metabolism. BAs are now recognized as signaling molecules that interact with both plasma membrane and nuclear receptors. Emerging evidence indicates that by interacting with these receptors, BAs regulate their own synthesis, glucose and energy homeostasis, and other important physiological events. Herein, we provide a comprehensive review of the actions of BAs on cardiovascular function. In the heart and the systemic circulation, BAs interact with plasma membrane G-protein-coupled receptors, for example, TGR5 and muscarinic receptors, and nuclear receptors, for example, the farnesoid (FXR) and pregnane (PXR) xenobiotic receptors. BA receptors are expressed in cardiovascular tissue, however, the mechanisms underlying BA-mediated regulation of cardiovascular function remain poorly understood. BAs reduce heart rate by regulating channel conductance and calcium dynamics in sino-atrial and ventricular cardiomyocytes and regulate vascular tone via both endothelium-dependent and -independent mechanisms. End-stage liver disease, obstructive jaundice, and intrahepatic cholestasis of pregnancy are prominent conditions in which elevated serum BAs alter vascular dynamics. This review focuses on BAs as newly recognized signaling molecules that modulate cardiovascular function.
authors.affiliation: Division of Gastroenterology and Hepatology, VA Maryland Health Care System and University of Maryland School of Medicine, Baltimore, MD, USA. skhurana@medicine.umaryland.edu
authors.forename: Sandeep
authors.initials: S
authors.lastname: Khurana
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Raufman
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Pallone
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002319:Cardiovascular System / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006339:Heart Rate; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001647:Bile Acids and Salts; D043562:Receptors, G-Protein-Coupled