{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:47:44Z","timestamp":1793346464062,"version":"4.5.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T00:00:00Z","timestamp":1570406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["11332003"],"award-info":[{"award-number":["11332003"]}],"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":["11572028"],"award-info":[{"award-number":["11572028"]}],"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":["11421202"],"award-info":[{"award-number":["11421202"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program in China","award":["2016YFC1101100"],"award-info":[{"award-number":["2016YFC1101100"]}]},{"name":"Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development","award":["#BX000282-09A2"],"award-info":[{"award-number":["#BX000282-09A2"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Blood flow patterns play an important role in the localization of atherosclerosis in the sense that low-flow state is pro-atherogenic, and helical flow is protective against atherosclerosis. Proprotein convertase subtilisin\/kexin type 9 (PCSK9) regulates cholesterol metabolism via low-density lipoprotein receptor (LDLr) degradation and is highly expressed in the atherosclerotic tissues. This study was designed to investigate the role of different blood flow patterns in the regulation of PCSK9 expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We designed an experimental model guider to generate stable helical flow. Our data showed that compared with normal flow, low-flow state induces whereas helical flow inhibits PCSK9 expression in the rabbit thoracic aorta in an inflammatory state. Our data also identified that TLR4-MyD88-NF-\u03baB signalling plays an important role in PCSK9 expression. On the other hand, TRIF pathway had almost no effect. Further studies showed that the signals downstream of NF-\u03baB, such as pro-inflammatory cytokines (IL-1\u03b2, IL-18, MCP-1, IL-6, TNF-\u03b1, IL-12, IFN\u03b3, and GM-CSF) directly influence PCSK9 expression. Interestingly, high fat diet further enhanced PCSK9 expression in an inflammatory milieu.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These observations suggest a link between abnormal flow patterns and PCSK9 expression in inflammatory states, which may qualify helical flow and pro-inflammatory cytokines as potential targets to treat PCSK9-related cardiovascular diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvz262","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T19:24:49Z","timestamp":1569957889000},"page":"1721-1732","source":"Crossref","is-referenced-by-count":69,"title":["Blood flow patterns regulate PCSK9 secretion via MyD88-mediated pro-inflammatory cytokines"],"prefix":"10.1093","volume":"116","author":[{"given":"Shijie","family":"Liu","sequence":"first","affiliation":[{"name":"College of Basic Medical Sciences, Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China"},{"name":"Department of Internal Medicine, Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, AR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China"},{"name":"Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1619-903X","authenticated-orcid":false,"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1490-8736","authenticated-orcid":false,"given":"Xianwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Central Arkansas Veterans Healthcare System and University of Arkansas for Medical Sciences, Little Rock, AR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China"},{"name":"Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sichang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurological 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