Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
Endothelial cell HSPA12B and yes-associated protein cooperatively regulate angiogenesis following myocardial infarction
Min Fan, … , David L. Williams, Chuanfu Li
Min Fan, … , David L. Williams, Chuanfu Li
Published August 13, 2020
Citation Information: JCI Insight. 2020;5(18):e139640. https://doi.org/10.1172/jci.insight.139640.
View: Text | PDF
Research Article Angiogenesis Vascular biology

Endothelial cell HSPA12B and yes-associated protein cooperatively regulate angiogenesis following myocardial infarction

  • Text
  • PDF
Abstract

Angiogenesis is essential for cardiac functional recovery after myocardial infarction (MI). HSPA12B is predominately expressed in endothelial cells and required for angiogenesis. Yes-associated protein (YAP) plays an important role in tumor angiogenesis. This study investigated the cooperative role of HSPA12B and YAP in angiogenesis after MI. Silencing of either HSPA12B or YAP impaired hypoxia-promoted endothelial cell proliferation and angiogenesis. Deficiency of HSPA12B suppressed YAP expression and nuclear translocation after hypoxia. Knockdown of YAP attenuated hypoxia-stimulated HSPA12B nuclear translocation and abrogated HSPA12B-promoted endothelial cell angiogenesis. Mechanistically, hypoxia induced an interaction between endothelial HSPA12B and YAP. ChIP assay showed that HSPA12B is a target gene of YAP/transcriptional enhanced associated domain 4 (TEAD4) and a coactivator in YAP-associated angiogenesis. In vivo studies using the MI model showed that endothelial cell–specific deficiency of HSPA12B (eHspa12b–/–) or YAP (eYap–/–) impaired angiogenesis and exacerbated cardiac dysfunction compared with WT mice. MI increased YAP expression and nuclear translocation in WT hearts but not eHspa12b–/– hearts. HSPA12B expression and nuclear translocation were upregulated in WT MI hearts but not eYap–/– MI myocardium. Our data demonstrate that endothelial HSPA12B is a target and coactivator for YAP/TEAD4 and cooperates with YAP to regulate endothelial angiogenesis after MI.

Authors

Min Fan, Kun Yang, Xiaohui Wang, Yana Wang, Fei Tu, Tuanzhu Ha, Li Liu, David L. Williams, Chuanfu Li

×

Figure 2

siRNA silencing of HSPA12B or YAP attenuates hypoxia-induced endothelial cell proliferation, migration, and angiogenesis.

Options: View larger image (or click on image) Download as PowerPoint
siRNA silencing of HSPA12B or YAP attenuates hypoxia-induced endothelial...
HUVECs were transfected with siRNA specific for HSPA12B (siHSPA12B) or for YAP (siYAP). Scrambled siRNA served as control (siNC). Twenty-four hours after transfection, the cells were subjected to hypoxia or normoxia. Cell proliferation was measured by Edu incorporation (n = 3) (A) and MTT assay (n = 4) (B) (scale bar: 400 μm). (C) Cell migration was examined by wound-healing assay (n = 3) (scale bar: 1000 μm). (D) The levels of Ang1 (n = 3), VEGF (n = 4), and VEGFR2 (n = 3) were examined by Western blot. GAPDH was used as loading control. Comparisons of data between groups were made using 1-way ANOVA followed by Tukey’s procedure. *P < 0.05, **P < 0.01, ***P < 0.001 compared with indicated groups. HUVECs, human umbilical vein endothelial cells; YAP, yes-associated protein; Edu, 5-ethynyl-2-deoxyuridine.

Copyright © 2025 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts