{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:09:57Z","timestamp":1767866997008,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,5,23]],"date-time":"2012-05-23T00:00:00Z","timestamp":1337731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Anatomical Record"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Metastatic calcification of cardiac valves is a common complication in patients affected by chronic renal failure. In this study, primary bovine aortic valve interstitial cells (AVICs) were subjected to pro\u2010calcific treatments consisting in cell stimulation with (i) elevated inorganic phosphate (Pi = 3 mM), to simulate hyperphosphatemic conditions; (ii) bacterial endotoxin lipopolysaccharide (LPS), simulating direct effects by microbial agents; and (iii) conditioned media (CM) derived from cultures of either LPS\u2010stimulated heterogenic macrophages (commercial murine RAW264.7 cells) or LPS\u2010stimulated fresh allogenic monocytes\/macrophages (bCM), simulating consequent inflammatory responses, alone or combined. Compared to control cultures, spectrophotometric assays revealed shared treatment\u2010dependent higher values of both calcium amounts and alkaline phosphatase activity for cultures involving the presence of elevated Pi. Ultrastructurally, shared peculiar pro\u2010calcific degeneration patterns were exhibited by AVICs from these latter cultures irrespectively of the additional treatments. Disappearance of all cytomembranes and concurrent formation of material showing positivity to Cuprolinic Blue and co\u2010localizing with silver precipitation were followed by the outcropping of such a material, which transformed in layers outlining the dead cells. Subsequent budding of these layers resulted in the formation of bubbling bodies and concentrically laminated calcospherulae mirroring those in actual soft tissue calcification. In conclusion, the <jats:italic>in vitro<\/jats:italic> models employed appear to be reliable tools for simulating metastatic calcification and indicate that hyperphosphatemic\u2010like conditions could trigger valve calcification <jats:italic>per se<\/jats:italic>, with LPS and allogenic macrophage\u2010derived secretory products acting as possible calcific enhancers <jats:italic>via<\/jats:italic> inflammatory responses. Anat Rec, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ar.22494","type":"journal-article","created":{"date-parts":[[2012,5,23]],"date-time":"2012-05-23T10:50:26Z","timestamp":1337770226000},"page":"1117-1127","source":"Crossref","is-referenced-by-count":11,"title":["Ultrastructural and Spectrophotometric Study on the Effects of Putative Triggers on Aortic Valve Interstitial Cells in <i>In Vitro<\/i> Models Simulating Metastatic Calcification"],"prefix":"10.1002","volume":"295","author":[{"given":"Antonella","family":"Bonetti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto Della","family":"Mora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magali","family":"Contin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Tubaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Marchini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fulvia","family":"Ortolani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,5,23]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"341","article-title":"Calcific diseases: a concept","volume":"107","author":"Anderson HC","year":"1983","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2008.03.008"},{"key":"e_1_2_5_4_1","first-page":"318","article-title":"Prevalence and clinical consequences of elevated Ca x P product in hemodialysis patients","volume":"54","author":"Block GA","year":"2000","journal-title":"Clin Nephrol"},{"key":"e_1_2_5_5_1","first-page":"22","article-title":"Calcium\u2010acidic phospholipid\u2010phosphate complexes in human hydroxyapatite\u2010containing pathologic deposits","volume":"133","author":"Boskey AL","year":"1988","journal-title":"Am J Pathol"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.42.26159"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(03)01454-1"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000161997.24797.c0"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(02)04312-6"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.7.e10"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(97)00003-X"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-2-11"},{"key":"e_1_2_5_13_1","first-page":"869","article-title":"Tumor necrosis factor alpha promotes an osteoblast\u2010like phenotype in human aortic valve myofibroblasts: a potential regulatory mechanism of valvular calcification","volume":"16","author":"Kaden JJ","year":"2005","journal-title":"Int J Mol Med"},{"key":"e_1_2_5_14_1","first-page":"156","article-title":"Calcification of matrix vesicles in human aortic valve and aortic media","volume":"35","author":"Kim KM","year":"1976","journal-title":"Federation Proc"},{"key":"e_1_2_5_15_1","first-page":"1137","article-title":"Apoptosis and calcification","volume":"9","author":"Kim KM","year":"1995","journal-title":"Scanning Microsc"},{"key":"e_1_2_5_16_1","first-page":"357","article-title":"Ultrastructural study of calcification of human aortic valve","volume":"25","author":"Kim KM","year":"1971","journal-title":"Lab Invest"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.bor.0000209431.59226.46"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH09-12-0814"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e3281c55ef1"},{"key":"e_1_2_5_20_1","first-page":"353","article-title":"Calcification of human valve interstitial cells is dependent on alkaline phosphatase activity","volume":"14","author":"Mathieu P","year":"2005","journal-title":"J Heart Valve Dis"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00137.2007"},{"key":"e_1_2_5_22_1","first-page":"160","article-title":"Infective endocarditis in chronic hemodialysis patients: experience from Morocco","volume":"22","author":"Montasser D","year":"2011","journal-title":"Saudi J Kidney Dis Transpl"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/649558"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1992.tb02119.x"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365549709011831"},{"key":"e_1_2_5_26_1","first-page":"261","article-title":"Ultrastructural characterization of calcification onset and progression in subdermally implanted aortic valves. Histochemical and spectrometric data","volume":"22","author":"Ortolani F","year":"2007","journal-title":"Histol Histopathol"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/gye.43.1.44.45"},{"key":"e_1_2_5_28_1","first-page":"1131","article-title":"Malachite green and phthalocyanin\u2010silver reactions reveal acidic phospholipid involvement in calcification of porcine aortic valves in rat subdermal model","volume":"18","author":"Ortolani F","year":"2003","journal-title":"Histol Histopathol"},{"key":"e_1_2_5_29_1","first-page":"135","article-title":"Pro\u2010calcific responses by aortic valve interstitial cells in a novel in vitro model simulating dystrophic calcification","volume":"115","author":"Ortolani F","year":"2010","journal-title":"Ital J Anat Embryol"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021347909622"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.174342"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/13.8.2037"},{"key":"e_1_2_5_33_1","first-page":"43","article-title":"Histological evaluation of autophagic cell death in calcified aortic valve stenosis","volume":"15","author":"Somers P","year":"2006","journal-title":"J Heart Valve Dis"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh2401.101070"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2006.00696.x"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc0502.102969"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1081\/JDI-200051837"},{"key":"e_1_2_5_38_1","first-page":"12","article-title":"Ultrastructural substrates of dystrophic calcification in porcine bioprosthetic valve failure","volume":"119","author":"Valente M","year":"1985","journal-title":"Am J Pathol"},{"key":"e_1_2_5_39_1","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1177\/089686080902902S01","article-title":"Vascular and other tissue calcification in peritoneal dialysis patients","volume":"29","author":"Wang AYM","year":"2009","journal-title":"Perit Dial Int"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1086\/649557"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117205"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.7.4404"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2009.08.025"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2007.01.003"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.09.052"}],"container-title":["The Anatomical Record"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Far.22494","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ar.22494","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:25:26Z","timestamp":1759940726000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/ar.22494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,23]]},"references-count":44,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2012,7]]}},"alternative-id":["10.1002\/ar.22494"],"URL":"https:\/\/doi.org\/10.1002\/ar.22494","archive":["Portico"],"relation":{},"ISSN":["1932-8486","1932-8494"],"issn-type":[{"value":"1932-8486","type":"print"},{"value":"1932-8494","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,23]]}}}