{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T17:03:24Z","timestamp":1789232604433,"version":"build-2803163510"},"reference-count":56,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32030053"],"award-info":[{"award-number":["32030053"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["91857112"],"award-info":[{"award-number":["91857112"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Key R&D Program of China administered by Chinese Ministry of Science and Technology","award":["2018YFA0800301"],"award-info":[{"award-number":["2018YFA0800301"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32150710522"],"award-info":[{"award-number":["32150710522"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,8]]},"abstract":"<jats:p>HDL cholesterol (HDL-C) predicts risk of cardiovascular disease (CVD), but the factors regulating HDL are incompletely understood. Emerging data link CVD risk to decreased HDL-C in 8% of the world population and 40% of East Asians who carry an SNP of aldehyde dehydrogenase 2 (ALDH2) rs671, responsible for alcohol flushing syndrome; however, the underlying mechanisms remain unknown. We found significantly decreased HDL-C with increased hepatosteatosis in ALDH2-KO (AKO), ALDH2\/LDLR\u2013double KO (ALKO), and ALDH2 rs671\u2013knock-in (KI) mice after consumption of a Western diet. Metabolomics identified ADP-ribose as the most significantly increased metabolites in the ALKO mouse liver. Moreover, ALDH2 interacted with poly(ADP-ribose) polymerase 1 (PARP1) and attenuated PARP1 nuclear translocation to downregulate poly(ADP-ribosyl)ation of liver X receptor \u03b1 (LXR\u03b1), leading to an upregulation of ATP-binding cassette transporter A1 (ABCA1) and HDL biogenesis. Conversely, AKO or ALKO mice exhibited lower HDL-C with ABCA1 downregulation due to increased nuclear PARP1 and upregulation of LXR\u03b1 poly(ADP-ribosyl)ation. Consistently, PARP1 inhibition rescued ALDH2 deficiency\u2013induced fatty liver and elevated HDL-C in AKO mice. Interestingly, KI mouse or human liver tissues showed ABCA1 downregulation with increased nuclear PARP1 and LXR\u03b1 poly(ADP-ribosyl)ation. Our study uncovered a key role of ALDH2 in HDL biogenesis through the LXR\u03b1\/PARP1\/ABCA1 axis, highlighting a potential therapeutic strategy in CVD.<\/jats:p>","DOI":"10.1172\/jci.insight.155869","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T08:36:17Z","timestamp":1649406977000},"source":"Crossref","is-referenced-by-count":19,"title":["Aldehyde dehydrogenase 2 and PARP1 interaction modulates hepatic HDL biogenesis by LXR\u03b1-mediated ABCA1 expression"],"prefix":"10.1172","volume":"7","author":[{"given":"Luxiao","family":"Li","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Zhong","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, ShanghaiTech University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Liang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, ShanghaiTech University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Xu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiting","family":"Chen","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhen","family":"Tao","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-1560","authenticated-orcid":true,"given":"Huiyong","family":"Yin","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China."},{"name":"School of Life Science and Technology, ShanghaiTech University, Shanghai, China."},{"name":"Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03392-8"},{"issue":"11","key":"B2","first-page":"e596","article-title":"2019 ACC\/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology\/American Heart Association task force on clinical practice guidelines","volume":"140","author":"Arnett","year":"2019","journal-title":"Circulation"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2019.0295"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0190-7"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1021\/cr200084z"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.308903"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.300760"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313238"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nature10486"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0144-3"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.312617"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2017.115"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000170946.56981.5c"},{"key":"B14","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-981-15-6082-8_6","article-title":"ABC transporters, cholesterol efflux, and implications for cardiovascular diseases","volume":"1276","author":"Wang","year":"2020","journal-title":"Adv Exp Med Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30163"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.475715"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0037-x"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1101\/gad.183509.111"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1963"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.06.016"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2021.101117"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.726729"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.50042"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2013"},{"key":"B25","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/978-981-13-6260-6_3","article-title":"ALDH2 and cardiovascular disease","volume":"1193","author":"Chen","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"B26","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/978-981-13-6260-6_15","article-title":"Aldehyde dehydrogenase 2 (ALDH2) and aging: is there a sensible link?","volume":"1193","author":"Wu","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq253"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa352"},{"issue":"1","key":"B29","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1172\/JCI122064","article-title":"Acetaldehyde dehydrogenase 2 interactions with LDLR and AMPK regulate foam cell formation","volume":"129","author":"Zhong","year":"2019","journal-title":"J Clin Invest"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3978"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/ng.834"},{"issue":"1","key":"B32","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1172\/JCI125433","article-title":"Not just correlative: a new pathway defines how an ALDH2 SNP contributes to atherosclerosis","volume":"129","author":"Gibb","year":"2019","journal-title":"J Clin Invest"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101919"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/art.41733"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2812"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.11.020"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1510757112"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-5688(11)70885-6"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1658"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60312-2"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.11.001"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-020-01787-5"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.184"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10206"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000166616.86723.d0"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200523915"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27352"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200112810"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.05.032"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.101069"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000126889.97626.B8"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa064278"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1177\/2047487318816495"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903387"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-0086-7"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/nm1471"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/155869\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:21:10Z","timestamp":1779150070000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/155869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,8]]},"references-count":56,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4,8]]},"published-print":{"date-parts":[[2022,4,8]]}},"alternative-id":["10.1172\/jci.insight.155869"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.155869","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,8]]},"article-number":"e155869"}}