Work

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

Year: 2020

Type: article

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.

Source: JCI Insight

DOI: 10.1172/jci.insight.139640