000164006 001__ 164006
000164006 005__ 20251127152544.0
000164006 0247_ $$2doi$$a10.1093/toxsci/kfs313
000164006 0248_ $$2sideral$$a78027
000164006 037__ $$aART-2013-78027
000164006 041__ $$aeng
000164006 100__ $$aMartín-Pardillos A$$uUniversidad de Zaragoza
000164006 245__ $$aArsenic increases Pi-mediated vascular calcification and induces premature senescence in vascular smooth muscle cells.
000164006 260__ $$c2013
000164006 5060_ $$aAccess copy available to the general public$$fUnrestricted
000164006 5203_ $$aSeveral mechanisms have been proposed to explain the vascular toxicity of arsenic. Some of them are described in this work, such as stress-induced premature senescence (SIPS), dedifferentiation, and medial vascular calcification, and they all affect vascular smooth muscle cells (VSMC). Rat aortic VSMC were treated with 1–100µM of either sodium arsenate (AsV), sodium arsenite (AsIII), monomethylarsonic acid, or dimethylarsinic acid. None of the treatments induced VSMC calcification in the presence of 1mM inorganic phosphate (Pi), but 1µM AsIII did increase calcification when induced with 2.5mM Pi. A lactate dehydrogenase assay revealed that this increase was explained by a rise in cytotoxicity due to simultaneous incubation with 1µM AsIII and 2.5mM Pi. This calcification increase was also observed in the aortas of a vascular calcification model: 5/6 nephrectomized rats fed with a high Pi diet and treated with vitamin D3. Several known mechanisms that might explain arsenic toxicity in our experimental model were discarded: apoptosis, oxidative stress, and inflammasome activation. Nevertheless, both senescence-associated β-galactosidase activity and p21 expression were increased by AsIII, which reveals the induction of SIPS. AsIII also caused dedifferentiation of VSMC, as shown by the reduced expression of the VSMC markers SM22α and calponin. Senescence and gene expression were also observed in the aortas of healthy rats treated with 50 ppm AsV in drinking water for 1 month. In conclusion, both premature senescence in aortic VSMC with phenotypic dedifferentiation and the increase of Pi-induced calcification are novel mechanisms of arsenic vasculotoxicity.
000164006 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000164006 590__ $$a4.478$$b2013
000164006 591__ $$aTOXICOLOGY$$b10 / 87 = 0.115$$c2013$$dQ1$$eT1
000164006 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000164006 700__ $$0(orcid)0000-0003-2907-0427$$aSosa C$$uUniversidad de Zaragoza
000164006 700__ $$0(orcid)0000-0003-3457-323X$$aSorribas V$$uUniversidad de Zaragoza
000164006 7102_ $$11000$$2807$$aUniversidad de Zaragoza$$bDpto. Anat.Pat.Med.Leg.For.To.$$cArea Toxicología
000164006 773__ $$g131, 2 (2013), 641-653$$pToxicol. sci.$$tTOXICOLOGICAL SCIENCES$$x1096-6080
000164006 8564_ $$s1803685$$uhttps://zaguan.unizar.es/record/164006/files/texto_completo.pdf$$yPostprint
000164006 8564_ $$s734708$$uhttps://zaguan.unizar.es/record/164006/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000164006 909CO $$ooai:zaguan.unizar.es:164006$$particulos$$pdriver
000164006 951__ $$a2025-11-27-15:23:40
000164006 980__ $$aARTICLE