title: Apelin: A novel inhibitor of vascular calcification in chronic kidney disease.
abstract: BACKGROUND
  Vascular calcification (VC) is closely related to cardiovascular events in chronic kidney disease (CKD). Apelin has emerged as a potent regulator of cardiovascular function, but its role in VC during CKD remains unknown. We determined whether apelin plays a role in phosphate-induced mineralization of human aortic smooth muscle cells (HASMCs) and in adenine-induced CKD rats with aortic calcification.
  
  
  RESULTS
  In vitro, apelin-13 was found to inhibit calcium deposition in HASMCs (Pi(+) Apelin(+) group vs Pi(+) Apelin(-) group: 50.1 ± 6.21 ug/mg vs 146.67 ± 10.02 ug/mg protein, p = 0.012) and to suppress the induction of the osteoblastic transformation genes BMP-2, osteoprotegerin (OPG) and Cbfa1. This effect was mediated by interference of the sodium-dependent phosphate cotransporter (Pit-1) expression and phosphate uptake. In vivo, decreased plasma apelin levels (adenine(+) apelin(-) vs vehicle: 0.37 ± 0.09 ng/ml vs 0.68 ± 0.16 ng/ml, p = 0.003) and downregulation of APJ in the aorta were found in adenine-induced CKD rats with hyperphosphatemia (adenine(+) apelin(-) vs vehicle: 6.91 ± 0.23 mmoL/L vs 2.3 ± 0.07 mmoL/L, p = 0.001) and aortic calcification. Exogenous supplementation of apelin-13 normalized the level of the apelin/APJ system and significantly ameliorated aortic calcification, as well as the suppression of Runx2, OPG and Pit-1 expression.
  
  
  CONCLUSIONS
  Apelin ameliorates VC by suppressing osteoblastic differentiation of VSMCs through downregulation of Pit-1. These results suggest apelin may have potential therapeutic value for treatment of VC in CKD.
authors.affiliation: Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing 100050, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing 100050, China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing 100050, China.
authors.forename: Zong-Li
authors.initials: ZL
authors.lastname: Diao
authors.affiliation: Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, Beijing 100050, China. Electronic address: whysnowman@126.com.
authors.forename: Wen-Hu
authors.initials: WH
authors.lastname: Liu
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D061205:Vascular Calcification / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D053244:Osteoprotegerin; C493717:Runx2 protein, rat; C493588:Slc20a1 protein, rat; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; C506032:Tnfrsf11b protein, rat; C495199:apelin-13 peptide; D012313:RNA
keywords: Apelin; Chronic kidney disease; Pit-1; Vascular calcification