title: Endothelin-converting enzyme-1 inhibition and renoprotection in end-stage renal disease.
abstract: Endothelin is one of the most potent peptide vasoconstrictors thus far characterised. It is produced by the cleavage of its precursor big endothelin-1 by endothelin-converting enzyme-1 (ECE-1). The endothelin system which includes endothelin-1 (ET-1), ET receptors and ECE-1 is well characterised in the kidney and is known to play a key role in the pathogenesis of end-stage renal disease (ESRD). Therefore, inhibition of ECE-1 and antagonism of ET receptors represent potential therapeutic approaches for the treatment of ESRD. Here, we review the current literature on the localisation of ECE-1 in the normal kidney and how ECE-1 expression is altered in pathological conditions leading to ESRD. We also discuss the roles of neutral endopeptidase (NEP) and chymase in mediating the production of ET-1 in the kidney in ESRD. As such, we also discuss that complete inhibition of ET-1 production in the kidney requires the inhibition of ECE-1, NEP and chymase.
authors: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. Sanjaya.Kuruppu@monash.edu
authors: Sanjaya
authors: S
authors: Kuruppu
authors: Niwanthi W
authors: NW
authors: Rajapakse
authors: A Ian
authors: AI
authors: Smith
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053818:Chymases / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015260:Neprilysin / Q000378:metabolism
chemical_list: D016232:Endothelins; D004791:Enzyme Inhibitors; D053818:Chymases; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes