{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:24:59Z","timestamp":1788672299040,"version":"build-2803163510"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Angiocrine factors, mediating the endothelial-mural cell interaction in vascular wall construction as well as maintenance, are incompletely characterized. This study aims to investigate the role of endothelial cell\u2013derived FSTL1 (follistatin-like protein 1) in vascular homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>\n                      Using conditional knockout mouse models, we show that loss of FSTL1 in endothelial cells (\n                      <jats:italic>Fstl1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>ECKO<\/jats:italic>\n                      <\/jats:sup>\n                      ) led to an increase of pulmonary vascular resistance, resulting in the heart regurgitation especially with tricuspid valves. However, this abnormality was not detected in mutant mice with\n                      <jats:italic>Fstl1<\/jats:italic>\n                      knockout in smooth muscle cells or hematopoietic cells. We further showed that there was excessive \u03b1SMA (\u03b1-smooth muscle actin) associated with atrial endocardia, heart valves, veins, and microvessels after the endothelial FSTL1 deletion. There was also an increase in collagen deposition, as demonstrated in livers of\n                      <jats:italic>Fstl1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>ECKO<\/jats:italic>\n                      <\/jats:sup>\n                      mutants. The SMAD3 (mothers against decapentaplegic homolog 3) phosphorylation (pSMAD3) was significantly enhanced, and pSMAD3 staining was colocalized with \u03b1SMA in vein walls, suggesting the activation of TGF\u03b2 (transforming growth factor \u03b2) signaling in vascular mural cells of\n                      <jats:italic>Fstl1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>ECKO<\/jats:italic>\n                      <\/jats:sup>\n                      mice. Consistently, treatment with a TGF\u03b2 pathway inhibitor reduced the abnormal association of \u03b1SMA with the atria and blood vessels in\n                      <jats:italic>Fstl1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>ECKO<\/jats:italic>\n                      <\/jats:sup>\n                      mutant mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The findings imply that endothelial FSTL1 is critical for the homeostasis of vascular walls, and its insufficiency may favor cardiovascular fibrosis leading to heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.119.313901","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T05:00:23Z","timestamp":1581570023000},"page":"958-972","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["Angiocrine FSTL1 (Follistatin-Like Protein 1) Insufficiency Leads to Atrial and Venous Wall Fibrosis via SMAD3 Activation"],"prefix":"10.1161","volume":"40","author":[{"given":"Haijuan","family":"Jiang","sequence":"first","affiliation":[{"name":"From the Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Cam-Su Genomic Resources Center, Soochow University, Suzhou, China (H.J., L.Z., X. Liu, C.C., X. Li, T.L., Z.S., Y.H.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Cam-Su Genomic Resources Center, Soochow University, Suzhou, China (H.J., L.Z., X. Liu, C.C., X. Li, T.L., Z.S., Y.H.)"},{"name":"MOE Key Laboratory for Model Animal and Disease Study, Model Animal Research Institute, Nanjing University, China (L.Z., W.S., W.H., F.Z., Q.X., Z.Y., X.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelian","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Cam-Su Genomic Resources Center, Soochow University, Suzhou, China (H.J., L.Z., X. Liu, C.C., X. Li, T.L., Z.S., Y.H.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory for Model Animal and Disease Study, Model Animal Research Institute, Nanjing University, China (L.Z., W.S., W.H., F.Z., Q.X., Z.Y., X.G.)"},{"name":"Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, China (W.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiro","family":"Kato","sequence":"additional","affiliation":[{"name":"Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of M\u00fcnster, Faculty of Medicine, Germany (K.K., R.H.A.)"},{"name":"Department of Cardiology, Nagoya University Hospital, Japan (K.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuankai","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Cam-Su Genomic Resources Center, Soochow University, Suzhou, China (H.J., L.Z., X. 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