{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:58:12Z","timestamp":1790611092502,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007374","name":"University of Udine","doi-asserted-by":"publisher","award":["Research funding"],"award-info":[{"award-number":["Research funding"]}],"id":[{"id":"10.13039\/100007374","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Calcium-dependent cytosolic phospholipase A2\u03b1 (cPLA2\u03b1) had been previously found to be overexpressed by aortic valve interstitial cells (AVICs) subjected to in vitro calcific induction. Here, cPLA2\u03b1 expression was immunohistochemically assayed in porcine aortic valve leaflets (iAVLs) that had undergone accelerated calcification subsequent to 2- to 28-day-long implantation in rat subcutis. A time-dependent increase in cPLA2\u03b1-positive AVICs paralleled mineralization progression depending on dramatic cell membrane degeneration with the release of hydroxyapatite-nucleating acidic lipid material, as revealed by immunogold particles decorating organelle membranes in 2d-iAVLs, as well as membrane-derived lipid byproducts in 7d- to 28d-iAVLs. Additional positivity was detected for (i) pro-inflammatory IL-6, mostly exhibited by rat peri-implant cells surrounding 14d- and 28d-iAVLs; (ii) calcium-binding osteopontin, with time-dependent increase and no ossification occurrence; (iii) anti-calcific fetuin-A, mostly restricted to blood plasma within vessels irrorating the connective envelopes of 28d-iAVLs; (iv) early apoptosis marker annexin-V, limited to sporadic AVICs in all iAVLs. No positivity was found for either apoptosis executioner cleaved caspase-3 or autophagy marker MAP1. In conclusion, cPLA2\u03b1 appears to be a factor characterizing AVL calcification concurrently with a distinct still uncoded cell death form also in an animal model, as well as a putative target for the prevention and treatment of calcific valve diseases.<\/jats:p>","DOI":"10.3390\/ijms23041988","type":"journal-article","created":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T03:46:00Z","timestamp":1644810360000},"page":"1988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Calcium-Dependent Cytosolic Phospholipase A2\u03b1 as Key Factor in Calcification of Subdermally Implanted Aortic Valve Leaflets"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5028-8135","authenticated-orcid":false,"given":"Antonella","family":"Bonetti","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Udine, I-33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Contin","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Udine, I-33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Tonon","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Udine, I-33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Marchini","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Udine, I-33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5268-7201","authenticated-orcid":false,"given":"Fulvia","family":"Ortolani","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Udine, I-33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1111\/eci.12169","article-title":"Impact of hypertension and renin-angiotensin system inhibitors in aortic stenosis","volume":"43","author":"Capoulade","year":"2013","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1093\/eurheartj\/ehi248","article-title":"Extracellular matrix remodelling in human aortic valve disease: The role of matrix metalloproteinases and their tissue inhibitors","volume":"26","author":"Fondard","year":"2005","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1016\/j.jacc.2019.01.070","article-title":"Lipoprotein (a) and oxidized phospholipids promote valve calcification in patients with aortic stenosis","volume":"73","author":"Zheng","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.jacc.2008.05.043","article-title":"Dysregulation of antioxidant mechanisms contributes to increased oxidative stress in calcific aortic valvular stenosis in humans","volume":"52","author":"Miller","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3389\/fphys.2018.00201","article-title":"Toll-like receptors, inflammation, and calcific aortic valve disease","volume":"9","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.ijcard.2017.05.040","article-title":"Could circulating fetuin A be a biomarker of aortic valve stenosis?","volume":"249","author":"Zanobini","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.amjcard.2009.10.065","article-title":"Calcium metabolism in adults with severe aortic valve stenosis and preserved renal function","volume":"105","author":"Akat","year":"2010","journal-title":"Am. J. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/S0046-8177(03)00245-4","article-title":"Angiogenesis is involved in the pathogenesis of nonrheumatic aortic valve stenosis","volume":"34","author":"Soini","year":"2003","journal-title":"Hum. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.pbiomolbio.2016.02.002","article-title":"Osteogenesis in calcified aortic valve disease: From histopathological observation towards molecular understanding","volume":"122","author":"Liu","year":"2016","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_10","first-page":"1137","article-title":"Apoptosis and calcification","volume":"9","author":"Kim","year":"1995","journal-title":"Scanning Microsc."},{"key":"ref_11","first-page":"43","article-title":"Histological evaluation of autophagic cell death in calcified aortic valve stenosis","volume":"15","author":"Somers","year":"2006","journal-title":"J. Heart Valve Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ijcard.2013.09.012","article-title":"Aortic valvular interstitial cells apoptosis and calcification are mediated by TNF-related apoptosis-inducing ligand","volume":"169","author":"Galeone","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/pin.12074","article-title":"Fat cells and membranous fat necrosis of aortic valves: A clinicopathological study","volume":"63","author":"Matsukuma","year":"2013","journal-title":"Pathol. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1172\/JCI119265","article-title":"Increased cellular expression of matrix proteins that regulate mineralization is associated with calcification of native human and porcine xenograft bioprosthetic heart valves","volume":"99","author":"Srivatsa","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1136\/hrt.2005.075903","article-title":"Expression of bone-regulatory proteins in human valve allografts","volume":"92","author":"Shetty","year":"2006","journal-title":"Heart"},{"key":"ref_16","first-page":"156","article-title":"Calcification of matrix vesicles in human aortic valve and aortic media","volume":"35","author":"Kim","year":"1976","journal-title":"Fed. Proc."},{"key":"ref_17","first-page":"353","article-title":"Calcification of human valve interstitial cells is dependent on alkaline phosphatase activity","volume":"14","author":"Mathieu","year":"2005","journal-title":"J. Heart Valve Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.jacc.2013.08.1639","article-title":"New therapeutic targets for calcific aortic valve stenosis: The lipoprotein(a)-lipoprotein-associated phospholipase A2-oxidized phospholipid axis","volume":"63","author":"Hung","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.jacc.2013.05.105","article-title":"Elevated expression of lipoprotein-associated phospholipase A2 in calcific aortic valve disease: Implications for valve mineralization","volume":"63","author":"Mahmut","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_20","first-page":"191","article-title":"The role of phospholipids in biological calcification: Distribution of phospholipase activity in calcifying epiphyseal cartilage","volume":"90","author":"Wuthier","year":"1973","journal-title":"Clin. Orthop."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s000110050566","article-title":"Augmented prostaglandin E2 generation resulting from increased activities of cytosolic and secretory phospholipase A2 and induction of cyclooxygenase-2 in interleukin-1 beta-stimulated rat calvarial cells during the mineralizing phase","volume":"49","author":"Higashi","year":"2000","journal-title":"Inflamm. Res."},{"key":"ref_22","first-page":"78","article-title":"The quest for a medical treatment of aortic stenosis: Putative therapeutic targets","volume":"2","year":"2014","journal-title":"Eur. Med. J. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1093\/cvr\/cvx138","article-title":"Bioactive lipids in aortic valve stenosis-a possible link to atherosclerosis?","volume":"113","author":"Larsson","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1080\/gye.43.1.44.45","article-title":"Novel ultrastructural features as revealed by phthalocyanine reactions indicate cell priming for calcification in subdermally implanted aortic valves","volume":"43","author":"Ortolani","year":"2002","journal-title":"Connect. Tissue Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1023\/A:1021347909622","article-title":"Copper retention, calcium release and ultrastructural evidence indicate specific Cuprolinic Blue uptake and peculiar modifications in mineralizing aortic valves","volume":"34","author":"Ortolani","year":"2002","journal-title":"Histochem. J."},{"key":"ref_26","first-page":"1131","article-title":"Malachite green and phthalocyanine-silver reactions reveal acidic phospholipid involvement in calcification of porcine aortic valves in rat subdermal model","volume":"18","author":"Ortolani","year":"2003","journal-title":"Histol. Histopathol."},{"key":"ref_27","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","year":"2007","journal-title":"Histol. Histopathol."},{"key":"ref_28","first-page":"135","article-title":"Pro-calcific responses by aortic valve interstitial cells in a novel in vitro model simulating dystrophic calcification","volume":"115","author":"Ortolani","year":"2010","journal-title":"Ital. J. Anat. Embryol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.21037\/jtd.2019.04.78","article-title":"Ectopic mineralization in heart valves: New insights from in vivo and in vitro procalcific models and promising perspectives on noncalcifiable bioengineered valves","volume":"11","author":"Bonetti","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1002\/ar.22494","article-title":"Ultrastructural and spectrophotometric study on the effects of putative triggers on aortic valve interstitial cells in in vitro models simulating metastatic calcification","volume":"295","author":"Bonetti","year":"2012","journal-title":"Anat. Rec."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1369\/0022155416687760","article-title":"Survival-related autophagic activity versus procalcific death in cultured aortic valve interstitial cells treated with critical normophosphatemic-like phosphate concentrations","volume":"65","author":"Bonetti","year":"2017","journal-title":"J. Histochem. Cytochem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bonetti, A., Allegri, L., Baldan, F., Contin, M., Battistella, C., Damante, G., Marchini, M., and Ortolani, F. (2020). Critical involvement of calcium-dependent cytosolic phospholipase A2a in aortic valve interstitial cell calcification. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176398"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.4081\/ejh.2015.2505","article-title":"Carotenoids co-localize with hydroxyapatite, cholesterol, and other lipids in calcified stenotic aortic valves. Ex vivo Raman maps compared to histological patterns","volume":"59","author":"Bonetti","year":"2015","journal-title":"Eur. J. Histochem."},{"key":"ref_34","first-page":"143","article-title":"Biologic determinants of dystrophic calcification and osteocalcin deposition in glutaraldehyde-preserved porcine aortic valve leaflets implanted subcutaneously in rats","volume":"113","author":"Levy","year":"1983","journal-title":"Am. J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"23451","DOI":"10.1016\/S0021-9258(18)35856-3","article-title":"Interleukin-1 alpha induces the accumulation of cytosolic phospholipase A2 and the release of prostaglandin E2 in human fibroblasts","volume":"267","author":"Lin","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19891","DOI":"10.1074\/jbc.272.32.19891","article-title":"Prostaglandin E2 amplifies cytosolic phospholipase A2- and cyclooxygenase-2-dependent delayed prostaglandin E2 generation in mouse osteoblastic cells. Enhancement by secretory phospholipase A2","volume":"272","author":"Murakami","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/JLB.3MIR0220-270R","article-title":"Complement: Bridging the innate and adaptive immune systems in sterile inflammation","volume":"108","author":"Lo","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S385","DOI":"10.1016\/S0003-4975(01)02492-4","article-title":"Characterization of the immune response to valve bioprostheses and its role in primary tissue failure","volume":"71","author":"Human","year":"2001","journal-title":"Ann. Thorac. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/ejcts\/ezu501","article-title":"Differences in xenoreactive immune response and patterns of calcification of porcine and bovine tissues in \u03b1-Gal knock-out and wild-type mouse implantation models","volume":"48","author":"Kim","year":"2015","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1161\/CIRCULATIONAHA.105.549311","article-title":"Glutaraldehyde-fixed bioprosthetic heart valve conduits calcify and fail from xenograft rejection","volume":"114","author":"Manji","year":"2006","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.4049\/jimmunol.1000193","article-title":"Endothelial ICAM-1 protein induction is regulated by cytosolic phospholipase A2\u03b1 via both NF-\u03baB and CREB transcription factors","volume":"186","author":"Hadad","year":"2011","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1742-2094-7-42","article-title":"Cytosolic phospholipase A2 alpha amplifies early cyclooxygenase-2 expression, oxidative stress and MAP kinase phosphorylation after cerebral ischemia in mice","volume":"7","author":"Kishimoto","year":"2010","journal-title":"Neuroinflammation"},{"key":"ref_43","first-page":"827","article-title":"Phosphatase enzyme activity is retained in glutaraldehyde treated bioprosthetic heart valves","volume":"34","author":"Maranto","year":"1988","journal-title":"ASAIO Trans."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26066","DOI":"10.1074\/jbc.M109.073791","article-title":"Serotonergic 5-HT2B receptor controls tissue-nonspecific alkaline phosphatase activity in osteoblasts via eicosanoids and phosphatidylinositol-specific phospholipase C","volume":"285","author":"Baudry","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1161\/01.CIR.92.8.2163","article-title":"Osteopontin is expressed in human aortic valvular lesions","volume":"92","author":"Kuusisto","year":"1995","journal-title":"Circulation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1161\/01.ATV.17.3.547","article-title":"Detection of osteopontin in calcified human aortic valves","volume":"17","author":"Mohler","year":"1997","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0764-4469(99)80086-9","article-title":"Osteopontin is associated with bioprosthetic heart valve calcification in humans","volume":"320","author":"Shen","year":"1997","journal-title":"C. R. Acad. Sci. III"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1007\/s00223-013-9698-6","article-title":"Role of osteopontin in modulation of hydroxyapatite formation","volume":"93","author":"Hunter","year":"2013","journal-title":"Calcif. Tissue Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0169-6009(08)80225-5","article-title":"Osteopontin-hydroxyapatite interactions in vitro: Inhibition of hydroxyapatite formation and growth in a gelatin-gel","volume":"22","author":"Boskey","year":"1993","journal-title":"Bone Miner."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3109\/1354750X.2011.642407","article-title":"Dephosphorylation of circulating human osteopontin correlates with severe valvular calcification in patients with calcific aortic valve disease","volume":"17","author":"Sainger","year":"2012","journal-title":"Biomarkers"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1161\/01.CIR.0000070591.21548.69","article-title":"Human aortic valve calcification is associated with an osteoblast phenotype","volume":"107","author":"Rajamannan","year":"2003","journal-title":"Circulation"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s00109-014-1229-z","article-title":"BMP-2 and TGF-\u03b21 mediate biglycan-induced pro-osteogenic reprogramming in aortic valve interstitial cells","volume":"93","author":"Song","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E375","DOI":"10.1532\/hsf.2033","article-title":"Evidence of osteogenic regulation in calcific porcine aortic valves","volume":"21","author":"Lu","year":"2018","journal-title":"Heart Surg. Forum."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1161\/01.CIR.103.11.1522","article-title":"Bone formation and inflammation in cardiac valves","volume":"103","author":"Mohler","year":"2001","journal-title":"Circulation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s00428-007-0430-7","article-title":"Bone formation in cardiac valves: A histopathological study of 128 cases","volume":"450","author":"Steiner","year":"2007","journal-title":"Virchows Arch."},{"key":"ref_56","first-page":"193","article-title":"Systemic and local levels of fetuin-A in calcific aortic valve stenosis","volume":"20","author":"Kaden","year":"2007","journal-title":"Int. J. Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ijcard.2018.03.070","article-title":"Impact of Fetuin-A on progression of calcific aortic valve stenosis\u2014The COFRASA-GENERAC study","volume":"265","author":"Kubota","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/bs.acc.2018.12.003","article-title":"Clinical implications of fetuin-A","volume":"89","author":"Jirak","year":"2019","journal-title":"Adv. Clin. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0022-1759(95)00072-I","article-title":"A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V","volume":"184","author":"Vermes","year":"1995","journal-title":"J. Immunol. Methods"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5687","DOI":"10.4049\/jimmunol.161.10.5687","article-title":"Caspase-mediated inhibition of human cytosolic phospholipase A2 during apoptosis","volume":"161","author":"Schwandner","year":"1998","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1042\/bj3290369","article-title":"Inhibition of human cytosolic phospholipase A2 by human annexin V","volume":"329","author":"Buckland","year":"1998","journal-title":"Biochem. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10474","DOI":"10.1074\/jbc.272.16.10474","article-title":"Inhibition of cytosolic phospholipase A2 by annexin V in differentiated permeabilized HL-60 cells. Evidence of crucial importance of domain I type II Ca2+-binding site in the mechanism of inhibition","volume":"272","author":"Mira","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"35577","DOI":"10.1074\/jbc.M005648200","article-title":"The roles of annexins and types II and X collagen in matrix vesicle-mediated mineralization of growth plate cartilage","volume":"275","author":"Kirsch","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10310","DOI":"10.1074\/jbc.M708456200","article-title":"Collagen\/annexin V interactions regulate chondrocyte mineralization","volume":"283","author":"Kim","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1080\/15548627.2019.1628538","article-title":"PLA2G4A\/cPLA2-mediated lysosomal membrane damage leads to inhibition of autophagy and neurodegeneration after brain trauma","volume":"16","author":"Sarkar","year":"2020","journal-title":"Autophagy"},{"key":"ref_67","first-page":"523","article-title":"Onset and progression of experimental bioprosthetic heart valve calcification","volume":"52","author":"Schoen","year":"1985","journal-title":"Lab. Investig."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/1988\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:17:22Z","timestamp":1760134642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/1988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,11]]},"references-count":67,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23041988"],"URL":"https:\/\/doi.org\/10.3390\/ijms23041988","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,11]]}}}