{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:05:52Z","timestamp":1783631152758,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":296,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> This research is aimed at unravelling the intricate relationship between transient receptor potential vanilloid 6 (TRPV6), protein kinase A (PKA), uncoupling protein 2 (UCP2), and atherosclerosis. By shedding light on the role of the TRPV6\/PKA\/UCP2 pathway in inhibiting inflammatory response and cell apoptosis in coronary atherosclerotic plaques, this study provides valuable insights into potential therapeutic targets for treating coronary artery disease (CAD).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We established animal and cell models of atherosclerosis. The expression of TRPV6 was measured using immunohistochemistry and immunofluorescence. Cytokine levels were detected by enzyme\u2010linked immunosorbent assay (ELISA). Cell viability and apoptosis ratio were measured using cell counting kit\u20108 (CCK\u20108) and flow cytometry. The binding relationship between TRPV6 and PKA was validated using chromatin immunoprecipitation (CHIP) and coimmunoprecipitation (CoIP). Finally, the expression of the TRPV6\/PKA\/UCP2 signaling pathway and apoptosis\u2010related factors was detected using western blot (WB) and quantitative real\u2010time polymerase chain reaction (qRT\u2010PCR).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> TRPV6 was significantly decreased in atherosclerosis mouse and cell model. CHIP and CoIP assays indicated that TRPV6 binds to PKA and positively regulated its expression in oxidized low\u2010density lipoprotein (ox\u2010LDL)\u2013treated human umbilical vein endothelial cells (HUVECs). Overexpression of TRPV6 significantly increased cell viability and inhibited apoptosis, whereas silencing TRPV6 had the opposite effect. Additionally, the overexpression of TRPV6 remarkably declined the expression of tumor necrosis factor\u2010alpha (TNF\u2010<jats:italic>\u03b1<\/jats:italic>), interleukin\u20106 (IL\u20106), and interleukin\u20101 beta (IL\u20101<jats:italic>\u03b2<\/jats:italic>). However, after silencing PKA, this effect was partially reversed, the cell viability and inflammatory response remarkably enhanced, and apoptosis significantly declined in oe\u2010TRPV6\u2009+\u2009si\u2010PKA group.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> In summary, our study demonstrated that TRPV6 inhibited apoptosis and inflammatory response in the atherosclerosis cell model through the regulation of the PKA\/UCP2 pathway.<\/jats:p>","DOI":"10.1155\/2024\/7053116","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T13:04:23Z","timestamp":1729688663000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Overexpression of TRPV6 Inhibits Coronary Atherosclerosis\u2013Related Inflammatory Response and Cell Apoptosis via the PKA\/UCP2 Pathway"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0614-8762","authenticated-orcid":false,"given":"Lei","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0155-2004","authenticated-orcid":false,"given":"Huiying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1823-7396","authenticated-orcid":false,"given":"Xuewen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.2991\/jegh.k.201217.001"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.537878"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00955-7"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-117"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2020.1747803"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11091423"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1093584"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2007.01.001"},{"key":"e_1_2_13_9_2","first-page":"775","article-title":"TRPV6 is associated with prognosis of ST-elevation acute myocardial infarction","volume":"50","author":"Zhang H.","year":"2020","journal-title":"Annals of Clinical and Laboratory Science"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.253807"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02521-3"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.05.008"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0809540"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6420425"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.723922"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10111746"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00698-1"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-018-0203-9"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-023-03038-9"},{"key":"e_1_2_13_20_2","volume-title":"Risk factors for coronary artery disease","author":"Brown J. 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