(Apo)Lipoprotein Profiling with Multi‐Omics Analysis Identified Medium‐HDL‐Targeting PSRC1 with Therapeutic Potential for Coronary Artery Disease
Abstract Identification of (apo)lipoprotein subclasses causally underpinning atherosclerosis may lead to identification of novel drug targets for treatment of atherosclerotic cardiovascular disease (ASCVD). In this study, observational and genetic associations between (apo)lipoprotein profile and ca...
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| Format: | Article |
| Language: | English |
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Wiley
2025-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202413491 |
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| author | Yingmei Li Sihan Wang Ling Liu Hao Cai Yacan Huang Mingjing Gao Xiaogang Zhang Qingqing Wu Gaokun Qiu |
| author_facet | Yingmei Li Sihan Wang Ling Liu Hao Cai Yacan Huang Mingjing Gao Xiaogang Zhang Qingqing Wu Gaokun Qiu |
| author_sort | Yingmei Li |
| collection | DOAJ |
| description | Abstract Identification of (apo)lipoprotein subclasses causally underpinning atherosclerosis may lead to identification of novel drug targets for treatment of atherosclerotic cardiovascular disease (ASCVD). In this study, observational and genetic associations between (apo)lipoprotein profile and carotid intima‐media thickness‐assessed atherosclerosis, and risks of coronary artery disease (CAD) and ischemic stroke (IS) are assessed, using data from the UK Biobank study, with further exploration of potential drug target for these two ASCVD subtypes through multi‐omics analysis integrating genetic, transcriptomic, and proteomic data. Cholesteryl ester content in medium high‐density lipoprotein causally protective of atherosclerosis is identified, plus a target gene, PSRC1, with therapeutic potential for CAD, but not IS, supported by consistent evidence from multi‐omics layers of data, which also reveals that such therapeutic potential may be through downregulation of circulating proteins including TRP1, GRNs, and Pla2g12b, and upregulation of Neo1. The results provide strong evidence as well as mechanistic clues of PSRC1’s therapeutic potential for CAD. |
| format | Article |
| id | doaj-art-5382f941790d4e53aa57368d0f774bd6 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-5382f941790d4e53aa57368d0f774bd62025-08-20T02:26:45ZengWileyAdvanced Science2198-38442025-04-011215n/an/a10.1002/advs.202413491(Apo)Lipoprotein Profiling with Multi‐Omics Analysis Identified Medium‐HDL‐Targeting PSRC1 with Therapeutic Potential for Coronary Artery DiseaseYingmei Li0Sihan Wang1Ling Liu2Hao Cai3Yacan Huang4Mingjing Gao5Xiaogang Zhang6Qingqing Wu7Gaokun Qiu8Ministry of Education and State Key Laboratory of Environmental Health (Incubating) School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaMinistry of Education and State Key Laboratory of Environmental Health (Incubating) School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaMinistry of Education and State Key Laboratory of Environmental Health (Incubating) School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaMinistry of Education and State Key Laboratory of Environmental Health (Incubating) School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaMinistry of Education and State Key Laboratory of Environmental Health (Incubating) School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaMinistry of Education and State Key Laboratory of Environmental Health (Incubating) School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaSCIEX Application Support Center Shanghai 200050 ChinaDepartment of Cardiology Zhongnan Hospital of Wuhan University Wuhan 430062 ChinaMinistry of Education and State Key Laboratory of Environmental Health (Incubating) School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaAbstract Identification of (apo)lipoprotein subclasses causally underpinning atherosclerosis may lead to identification of novel drug targets for treatment of atherosclerotic cardiovascular disease (ASCVD). In this study, observational and genetic associations between (apo)lipoprotein profile and carotid intima‐media thickness‐assessed atherosclerosis, and risks of coronary artery disease (CAD) and ischemic stroke (IS) are assessed, using data from the UK Biobank study, with further exploration of potential drug target for these two ASCVD subtypes through multi‐omics analysis integrating genetic, transcriptomic, and proteomic data. Cholesteryl ester content in medium high‐density lipoprotein causally protective of atherosclerosis is identified, plus a target gene, PSRC1, with therapeutic potential for CAD, but not IS, supported by consistent evidence from multi‐omics layers of data, which also reveals that such therapeutic potential may be through downregulation of circulating proteins including TRP1, GRNs, and Pla2g12b, and upregulation of Neo1. The results provide strong evidence as well as mechanistic clues of PSRC1’s therapeutic potential for CAD.https://doi.org/10.1002/advs.202413491(apo)lipoprotein profilingatherosclerotic cardiovascular diseasecarotid intima‐media thicknesscolocalizationmendelian randomizationmulti‐omics |
| spellingShingle | Yingmei Li Sihan Wang Ling Liu Hao Cai Yacan Huang Mingjing Gao Xiaogang Zhang Qingqing Wu Gaokun Qiu (Apo)Lipoprotein Profiling with Multi‐Omics Analysis Identified Medium‐HDL‐Targeting PSRC1 with Therapeutic Potential for Coronary Artery Disease Advanced Science (apo)lipoprotein profiling atherosclerotic cardiovascular disease carotid intima‐media thickness colocalization mendelian randomization multi‐omics |
| title | (Apo)Lipoprotein Profiling with Multi‐Omics Analysis Identified Medium‐HDL‐Targeting PSRC1 with Therapeutic Potential for Coronary Artery Disease |
| title_full | (Apo)Lipoprotein Profiling with Multi‐Omics Analysis Identified Medium‐HDL‐Targeting PSRC1 with Therapeutic Potential for Coronary Artery Disease |
| title_fullStr | (Apo)Lipoprotein Profiling with Multi‐Omics Analysis Identified Medium‐HDL‐Targeting PSRC1 with Therapeutic Potential for Coronary Artery Disease |
| title_full_unstemmed | (Apo)Lipoprotein Profiling with Multi‐Omics Analysis Identified Medium‐HDL‐Targeting PSRC1 with Therapeutic Potential for Coronary Artery Disease |
| title_short | (Apo)Lipoprotein Profiling with Multi‐Omics Analysis Identified Medium‐HDL‐Targeting PSRC1 with Therapeutic Potential for Coronary Artery Disease |
| title_sort | apo lipoprotein profiling with multi omics analysis identified medium hdl targeting psrc1 with therapeutic potential for coronary artery disease |
| topic | (apo)lipoprotein profiling atherosclerotic cardiovascular disease carotid intima‐media thickness colocalization mendelian randomization multi‐omics |
| url | https://doi.org/10.1002/advs.202413491 |
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