{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:08:49Z","timestamp":1785150529084,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":245,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["2022SF-276"],"award-info":[{"award-number":["2022SF-276"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018625","name":"Science and Technology Innovation Plan Of Shanghai Science and Technology Commission","doi-asserted-by":"publisher","award":["21S11906000"],"award-info":[{"award-number":["21S11906000"]}],"id":[{"id":"10.13039\/501100018625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800341"],"award-info":[{"award-number":["81800341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070402"],"award-info":[{"award-number":["82070402"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Calcific aortic valve disease (CAVD) is a prevalent valvular heart disease characterized by the fibrocalcific remodeling of the aortic valves, leading to significant health issues among the elderly population worldwide. The aberrant expression of long noncoding RNAs (lncRNAs) is closely associated with the pathogenesis of various diseases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods and Results:<\/jats:bold>\n                    A total of 241 differentially expressed lncRNAs were identified in calcified aortic valve tissues (fold change of \u2265\u20092 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009value &lt; 0.05), including 65 upregulated and 176 downregulated lncRNAs. The expression of the Top 5 upregulated lncRNAs was monitored during the calcification of valvular interstitial cell (VIC). Notably, the expression of lnc\u2010PRDM8\u20103 and lnc\u2010COL6A1\u20106 in VICs increased significantly after calcification induction and was sustained at high levels. Inhibition of lnc\u2010COL6A1\u20106, but not lnc\u2010PRDM8\u20103, obviously alleviated the calcification of VICs, as evidenced by a marked reduction in calcium deposition, decreased alkaline phosphatase activity, and downregulated expression of Runx2 and OPN. Bioinformatic analysis predicted that lnc\u2010COL6A1\u20106 might serve as a competing endogenous RNA for 11 miRNAs, potentially regulating the expression of 784 target genes. Among these, the Top 50 target genes were found to be significantly enriched in autophagy\u2010related biological processes. Consistently, elevated levels of the autophagic markers Beclin 1 and LC3\n                    <jats:italic>\u03b2<\/jats:italic>\n                    were detected in calcified aortic valve tissues. Inhibition of lnc\u2010COL6A1\u20106 significantly reduced autophagic flux in VICs under calcification\u2010inducing conditions. Importantly, pharmacological inhibition of autophagy using chloroquine abolished the anticalcific effects of lnc\u2010COL6A1\u20106 knockdown.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    The present study identified a lnc\u2010COL6A1\u20106\u2010mediated miRNA\u2013mRNA regulatory network in aortic valve calcification. Knockdown of lnc\u2010COL6A1\u20106 could mitigate VIC calcification by attenuating autophagic activity, highlighting its potential as a therapeutic target for CAVD.\n                  <\/jats:p>","DOI":"10.1155\/cdr\/2277191","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T11:52:48Z","timestamp":1756900368000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inhibition of lnc\u2010COL6A1\u20106\u2010Alleviated Osteogenic Differentiation of Valvular Interstitial Cells During Aortic Valve Calcification"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3016-9426","authenticated-orcid":false,"given":"Ying","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2251-4590","authenticated-orcid":false,"given":"Fan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4954-4414","authenticated-orcid":false,"given":"Quangong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6934-491X","authenticated-orcid":false,"given":"Jingwen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1115-2259","authenticated-orcid":false,"given":"Xiangyang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6857-0953","authenticated-orcid":false,"given":"Yang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2607-0943","authenticated-orcid":false,"given":"Xian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0074-7042","authenticated-orcid":false,"given":"Zhigang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1641-4007","authenticated-orcid":false,"given":"Zhiyun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4001-5077","authenticated-orcid":false,"given":"Guokun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.066822"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2024.04.011"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2023.10.012"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.033125"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001254"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2013.72"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-023-00845-7"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.71813"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.12070"},{"key":"e_1_2_12_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04177-6"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad117"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03342-x"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncrna.2024.06.002"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncrna.2023.03.006"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-024-02327-7"},{"key":"e_1_2_12_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2020-001471"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26670"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11748-020-01441-z"},{"key":"e_1_2_12_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2022.06.009"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010010"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1031"},{"key":"e_1_2_12_22_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202403109R"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.024270"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-7-520"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz757"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.065213"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01256-5"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1046"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155337"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2016.12.005"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2019.05.051"},{"key":"e_1_2_12_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx180"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0003-4"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13804"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2315893"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.92771"},{"key":"e_1_2_12_37_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061486"},{"key":"e_1_2_12_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab267"},{"key":"e_1_2_12_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad077"}],"container-title":["Cardiovascular Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/cdr\/2277191","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/cdr\/2277191","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/cdr\/2277191","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T17:49:50Z","timestamp":1773769790000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/cdr\/2277191"}},"subtitle":[],"editor":[{"given":"Youakim","family":"Saliba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1155\/cdr\/2277191"],"URL":"https:\/\/doi.org\/10.1155\/cdr\/2277191","archive":["Portico"],"relation":{},"ISSN":["1755-5914","1755-5922"],"issn-type":[{"value":"1755-5914","type":"print"},{"value":"1755-5922","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2025-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2277191"}}