Proteomics

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ZEB2 protects the heart from ischemic damage


ABSTRACT: infarct size and subsequent deterioration in function. The identification of factors that enhance cardiac repair by the restoration of the vascular network is, therefore, of great significance. Here, we show that the transcription factor Zinc finger E-box-binding homeobox 2 (ZEB2) is increased in stressed cardiomyocytes and induces a cardioprotective cross-talk between cardiomyocytes and endothelial cells to enhance angiogenesis after ischemia. Single-cell sequencing indicates ZEB2 to be enriched in injured cardiomyocytes. Cardiomyocyte-specific deletion of ZEB2 results in impaired cardiac contractility and infarct healing post-myocardial infarction (post-MI), while cardiomyocyte-specific ZEB2 overexpression improves cardiomyocyte survival and cardiac function. We identified Thymosin 4 (TMSB4) and Prothymosin (PTMA) as main paracrine factors released from cardiomyocytes to stimulate angiogenesis by enhancing endothelial cell migration, and whose regulation is validated in our in vivo models. Therapeutic delivery of ZEB2 to cardiomyocytes in the infarcted heart induces the expression of TMSB4 and PTMA, which enhances angiogenesis and prevents cardiac dysfunction. These findings reveal ZEB2 as a beneficial factor during ischemic injury, which may hold promise for the identification of new therapies.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart, Fetal Cardiomyocyte

SUBMITTER: Harmjan Vos  

LAB HEAD: Eva van Rooij

PROVIDER: PXD022212 | Pride | 2021-03-23

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20160408_F1_RM_MGV_25_C1.raw Raw
20160408_F1_RM_MGV_26_S1.raw Raw
20160408_F1_RM_MGV_27_C2.raw Raw
20160408_F1_RM_MGV_28_S2.raw Raw
20160408_F1_RM_MGV_29_C3.raw Raw
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Publications


The disruption in blood supply due to myocardial infarction is a critical determinant for infarct size and subsequent deterioration in function. The identification of factors that enhance cardiac repair by the restoration of the vascular network is, therefore, of great significance. Here, we show that the transcription factor Zinc finger E-box-binding homeobox 2 (ZEB2) is increased in stressed cardiomyocytes and induces a cardioprotective cross-talk between cardiomyocytes and endothelial cells t  ...[more]

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