title: Tumor necrosis factor-related apoptosis-inducing ligand and vascular calcification.
abstract: Vascular calcification is frequent in patients with chronic kidney disease. Osteoprotegerin (OPG, a soluble factor which blocks osteoclast differentiation) has recently been implicated in the genesis of vascular calcification. Given that OPG can bind the pro-apoptotic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we hypothesized that the TRAIL protein is involved in the formation of vascular calcification both in vitro and in vivo. Using an immunohistochemical approach, we evaluated TRAIL and OPG expression on aortic valves slides from non-uremic and uremic wild type and apolipoprotein knockout (Apo E(-/-) ) mice. We also tested the in vitro effects of TRAIL on cultured primary human vascular smooth muscle cells (hVSMC). We further assayed serum soluble TRAIL (sTRAIL) levels in hemodialysis patients and correlated them with vascular calcification scores. Our results demonstrated that: (i) TRAIL and OPG were expressed inside the atheroma plaque in non-uremic ApoE(-/-) mice, but not in wild type mice; and (ii) uremia enhanced the expression levels. TRAIL enhanced the phosphate-induced mineralization of hVSMCs in a dose-dependent manner. In clinical terms, we demonstrated that sTRAIL is depressed in the sera of hemodialysis patients, but was not correlated with vascular calcification. Our results suggest that TRAIL may be involved in the formation of vascular calcification in certain experimental settings; however, its role in chronic kidney disease patients requires further evaluation.
authors.affiliation: French National Institute of Health and Medical Research (INSERM), ERI-12 (EA 4292) and University of Picardie - Jules Verne, Amiens, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Chasseraud
authors.forename: Sophie
authors.initials: S
authors.lastname: Liabeuf
authors.forename: Anaïs
authors.initials: A
authors.lastname: Mozar
authors.forename: Romuald
authors.initials: R
authors.lastname: Mentaverri
authors.forename: Romuald
authors.initials: R
authors.lastname: Mentaveri
authors.forename: Michel
authors.initials: M
authors.lastname: Brazier
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.forename: Saïd
authors.initials: S
authors.lastname: Kamel
mesh_terms: D000368:Aged; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D002114:Calcinosis / Q000503:physiopathology*; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D053244:Osteoprotegerin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000473:pathology; D006435:Renal Dialysis / Q000379:methods; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D014511:Uremia / Q000503:physiopathology
chemical_list: D001057:Apolipoproteins E; D053244:Osteoprotegerin; D053221:TNF-Related Apoptosis-Inducing Ligand