{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T06:32:48Z","timestamp":1792477968673,"version":"4.5.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"national institute"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["# 82130012"],"award-info":[{"award-number":["# 82130012"]}],"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":["# 82300489"],"award-info":[{"award-number":["# 82300489"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008837","name":"Shanghai Chest Hospital","doi-asserted-by":"publisher","award":["# 2022YNJCQ03"],"award-info":[{"award-number":["# 2022YNJCQ03"]}],"id":[{"id":"10.13039\/501100008837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Vascular smooth muscle cell (VSMC) plasticity is a state in which VSMCs undergo phenotypic switching from a quiescent contractile phenotype into other functionally distinct phenotypes. Although emerging evidence suggests that VSMC plasticity plays critical roles in the development of vascular diseases, little is known about the key determinant for controlling VSMC plasticity and fate.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We found that smooth muscle cell-specific deletion of Lkb1 in tamoxifen-inducible Lkb1flox\/flox;Myh11-Cre\/ERT2 mice spontaneously and progressively induced aortic\/arterial dilation, aneurysm, rupture, and premature death. Single-cell RNA sequencing and imaging-based lineage tracing showed that Lkb1-deficient VSMCs transdifferentiated gradually from early modulated VSMCs to fibroblast-like and chondrocyte-like cells, leading to ossification and blood vessel rupture. Mechanistically, Lkb1 regulates polypyrimidine tract binding protein 1 (Ptbp1) expression and controls alternative splicing of pyruvate kinase muscle (PKM) isoforms 1 and 2. Lkb1 loss in VSMC results in an increased PKM2\/PKM1 ratio and alters the metabolic profile by promoting aerobic glycolysis. Treatment with PKM2 activator TEPP-46 rescues VSMC transformation and aortic dilation in Lkb1flox\/flox;Myh11-Cre\/ERT2 mice. Furthermore, we found that Lkb1 expression decreased in human aortic aneurysm tissue compared to control tissue, along with changes in markers of VSMC fate.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Lkb1, via its regulation of Ptbp1-dependent alterative splicing of PKM, maintains VSMC in contractile states by suppressing VSMC plasticity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvae187","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T11:47:06Z","timestamp":1724759226000},"page":"1780-1793","source":"Crossref","is-referenced-by-count":19,"title":["Regulation of Ptbp1-controlled alternative splicing of pyruvate kinase muscle by liver kinase B1 governs vascular smooth muscle cell plasticity <i>in vivo<\/i>"],"prefix":"10.1093","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8642-9040","authenticated-orcid":false,"given":"Zhaohua","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine , 241 Huaihai West Road, Shanghai 200030 ,","place":["China"]},{"name":"Center for Molecular and Translational Medicine, Georgia State University , 157 Decatur Street SE, Atlanta, GA 30303 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh","family":"Satyanarayana","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Medicine, Georgia State University , 157 Decatur Street SE, Atlanta, GA 30303 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Song","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Medicine, Georgia State University , 157 Decatur Street SE, Atlanta, GA 30303 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Medicine, Georgia State University , 157 Decatur Street SE, Atlanta, GA 30303 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojin","family":"You","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Medicine, Georgia State University , 157 Decatur Street SE, Atlanta, GA 30303 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixue","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Medicine, Georgia State University , 157 Decatur Street SE, Atlanta, GA 30303 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Mu","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Medicine, Georgia State University , 157 Decatur Street SE, Atlanta, GA 30303 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Ding","sequence":"additional","affiliation":[{"name":"Center for Molecular and Translational Medicine, Georgia State University , 157 Decatur Street SE, Atlanta, GA 30303 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine , 241 Huaihai West Road, Shanghai 200030 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hui","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of 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