Dataset Information

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

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			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

Cardiomyocytes stimulate angiogenesis after ischemic injury in a ZEB2-dependent manner.

Gladka Monika M MM Kohela Arwa A Molenaar Bas B Versteeg Danielle D Kooijman Lieneke L Monshouwer-Kloots Jantine J Kremer Veerle V Vos Harmjan R HR Huibers Manon M H MMH Haigh Jody J JJ Huylebroeck Danny D Boon Reinier A RA Giacca Mauro M van Rooij Eva E

Nature communications 20210104 1

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]

PMID: 33398012

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