{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:17:00Z","timestamp":1787991420472,"version":"build-2784847793"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":240,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Coronary atherosclerosis (CA) is a leading cause of cardiovascular morbidity and mortality worldwide. This study is aimed at identifying candidate plasma proteins and potential therapeutic targets for CA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a proteome\u2010wide Mendelian randomization (MR) analysis using integrated protein quantitative trait loci (pQTLs) and genome\u2010wide association study (GWAS) summary data. Forward two\u2010sample MR was first performed using cis\u2010pQTLs from the UK Biobank Pharma Proteomics Project (UKB\u2010PPP), followed by reverse MR analysis to exclude potential reverse causality. Bayesian colocalization analysis was conducted to ensure that the associations between proteins and CA were driven by shared genetic variants. Summary\u2010data\u2010based MR (SMR) combined with HEIDI testing was used to prioritize proteins and eliminate linkage bias. Significant proteins were cross\u2010referenced with a curated druggable genome to identify their potential therapeutic relevance. Cross\u2010platform validation was performed using the SomaScan\u2010based pQTL dataset from deCODE genetics. An oxidized low\u2010density lipoprotein (ox\u2010LDL)\u2013induced human umbilical vein endothelial cell (HUVEC) injury model was used for the evaluation of prioritized proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forward MR analysis using UKB\u2010PPP cis\u2010pQTL data identified 45 CA\u2010associated proteins (23 protective, 22 risk\u2010related; FDR\u2009&lt;\u20090.05), with no reverse causality observed. Five proteins\u2014PARP1, SDCCAG8, FST, FOLH1, and NCAN\u2014were prioritized through MR (FDR\u2009&lt;\u20090.05), colocalization analysis (PP.H4\u2009&gt;\u20090.50), and SMR analysis with HEIDI filtering (\n                      <jats:italic>p<\/jats:italic>\n                      _SMR &lt; 0.05;\n                      <jats:italic>p<\/jats:italic>\n                      _HEIDI &gt; 0.05). All five proteins were included in the druggable genome list, supporting their potential therapeutic relevance. PARP1 showed consistent associations across Olink and SomaScan platforms and was upregulated in an ox\u2010LDL\u2010induced HUVEC model as assessed by western blot.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identified PARP1, SDCCAG8, FST, FOLH1, and NCAN as genetically prioritized candidate proteins for CA, with PARP1 showing the most consistent evidence across analyses. Further validation and mechanistic studies are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/cdr\/7359278","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:51:18Z","timestamp":1787989878000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uncovering Potential Druggable Targets in Coronary Atherosclerosis: A Proteome\u2010Wide Mendelian Randomization Study With Cross\u2010Platform and Experimental Validation"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4664-5215","authenticated-orcid":false,"given":"Da","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2780-7122","authenticated-orcid":false,"given":"Haiyan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1985-7253","authenticated-orcid":false,"given":"Shengjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5168-325X","authenticated-orcid":false,"given":"Yanwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3027-4127","authenticated-orcid":false,"given":"Hao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5467-4849","authenticated-orcid":false,"given":"Zicheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10081938"},{"key":"e_1_2_15_2_2","first-page":"2982","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study","volume":"76","author":"Roth G. 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