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Angiocrine FSTL1 (Follistatin-Like Protein 1) Insufficiency Leads to Atrial and Venous Wall Fibrosis via SMAD3 Activation.
Jiang, Haijuan; Zhang, Luqing; Liu, Xuelian; Sun, Wei; Kato, Katsuhiro; Chen, Chuankai; Li, Xiao; Li, Taotao; Sun, Zhiliang; Han, Wencan; Zhang, Fujing; Xiao, Qi; Yang, Zhongzhou; Hu, Junhao; Qin, Zhihai; Adams, Ralf H; Gao, Xiang; He, Yulong.
Afiliação
  • Jiang H; 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
  • Zhang L; 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
  • Liu X; 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.).
  • Sun W; 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
  • Kato K; 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.).
  • Chen C; Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, China (W.S.).
  • Li X; Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, Germany (K.K., R.H.A.).
  • Li T; Department of Cardiology, Nagoya University Hospital, Japan (K.K.).
  • Sun Z; 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
  • Han W; 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
  • Zhang F; 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
  • Xiao Q; 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
  • Yang Z; 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.).
  • Hu J; 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.).
  • Qin Z; 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.).
  • Adams RH; 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.).
  • Gao X; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, China (J.H.).
  • He Y; The First Affiliated Hospital of Zhengzhou University, Academy of Medical Sciences, Zhengzhou University, China (Z.Q.).
Arterioscler Thromb Vasc Biol ; 40(4): 958-972, 2020 04.
Article em En | MEDLINE | ID: mdl-32078339
ABSTRACT

OBJECTIVE:

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-derived FSTL1 (follistatin-like protein 1) in vascular homeostasis. Approach and

Results:

Using conditional knockout mouse models, we show that loss of FSTL1 in endothelial cells (Fstl1ECKO) 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 Fstl1 knockout in smooth muscle cells or hematopoietic cells. We further showed that there was excessive αSMA (α-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 Fstl1ECKO mutants. The SMAD3 (mothers against decapentaplegic homolog 3) phosphorylation (pSMAD3) was significantly enhanced, and pSMAD3 staining was colocalized with αSMA in vein walls, suggesting the activation of TGFß (transforming growth factor ß) signaling in vascular mural cells of Fstl1ECKO mice. Consistently, treatment with a TGFß pathway inhibitor reduced the abnormal association of αSMA with the atria and blood vessels in Fstl1ECKO mutant mice.

CONCLUSIONS:

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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrose / Endotélio Vascular / Proteínas Relacionadas à Folistatina / Proteína Smad3 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Arterioscler Thromb Vasc Biol Assunto da revista: ANGIOLOGIA Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fibrose / Endotélio Vascular / Proteínas Relacionadas à Folistatina / Proteína Smad3 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Arterioscler Thromb Vasc Biol Assunto da revista: ANGIOLOGIA Ano de publicação: 2020 Tipo de documento: Article