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Abstract-The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidney, adrenals, and intestine. FXR may play an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol. In this study, we report that FXR is also expressed in rat pulmonary artery endothelial cells (EC) Key Words: farnesoid X receptor Ⅲ bile acids Ⅲ endothelin-1 Ⅲ endothelial cells Ⅲ gene regulation E ndothelin (ET)-1, a peptide of 21 amino acid residues, is the most potent vasoconstrictive substance known. 1 Originally isolated from porcine aortic EC, 1 ET-1 is now known to be 1 of a family of 3 mammalian vasoactive peptides that also includes ET-2 and ET-3. 2 ET is produced predominantly by endothelial cells (EC), but it is also produced by leukocytes, macrophages, smooth muscle cells (SMC), cardiomyocytes, and mesangial cells. 3 ET-1 produced in the EC is predominately released abluminally toward the muscular media suggesting a paracrine/autocrine role.,All 3 ETs bind to 2 types of receptors named ET A and ET B : in the cardiovascular system, ET A receptors are found in SMC and cardiac myocytes, whereas ET B receptors are primarily localized on EC and certain vascular SMC. 4 The binding of ET-1 to SMC ET A and ET B receptors leads to vasoconstriction. 3,5 On the other hand, the activation of endothelial ET B receptors by luminal ET-1 stimulates the release of NO and prostacyclin and plays a role in endothelium-dependent vasodilatation. 3,5 ET B receptors also mediate the pulmonary clearance of circulating ET-1 and the reuptake of ET-1 by EC. 3,5 The lungs represent a primary target for ET-1 effects and are a special site for ET-1 metabolic pathways. 5 A large body of evidence suggests that ET-1 may play an important role in the development of both primary and secondary pulmonary hypertension. 5 The endothelin system also plays an important role in the pathophysiology of a variety of other cardiovascular diseases including congestive heart failure, renal failure, and cerebrovascular disease. 6 Recently, vascular ET-1 has received increasing attention as a therapeutic target for the management of a number of vascular diseases. 7 Recent studies with reporter gene have revealed important insight into regulation of the human ppET-1 promoter. Regions essential for high basal levels of ppET-1 promoter activity in EC include binding sites for the factors activator protein (AP)-1 and GATA-2. 8 -10 An element binding the vascular endothelial zinc finger-1 protein and mediating EC-specific gene expression has recently been described in the ppET-1 promoter. 11 Recently nuclear factor (NF)-B and signal transducer and activator of transcription (STAT)-1 signaling has also been shown to be involved in ET-1 regulation in cells that are stimulated with either lipopolysaccharide (LPS) or cytokines. 12,13 Interestingly, ET-1 expression has been shown to be negatively regulated by several members of the nuclear receptor superfamily of ligand...

These results support the notion that vascular FXR may serve as a novel molecular target for manipulating the expression of eNOS for the treatment of vascular diseases.

The exploration of high performance electro-catalysts to facilitate oxygen evolution reaction (OER) in proton exchange membrane based water splitting is of vital importance for various energy storage devices and for sustainable hydrogen production.