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A surgical mouse model of neonatal pressure overload by transverse aortic constriction

Nature Protocols volume 16, pages 775–790 (2021)Cite this article

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Abstract

Cardiac disease is the main cause of death worldwide. Insufficient regeneration of the adult mammalian heart is a major driver of cardiac morbidity and mortality. Cardiac regeneration occurs in early postnatal mice, thus understanding mechanisms of mammalian cardiac regeneration could facilitate the development of novel therapeutic strategies. Here, we provide a detailed description of a neonatal mouse model of pressure overload by transverse aortic constriction (nTAC) that can be applied at postnatal days 1 and 7. We have previously used this model to demonstrate that mice are able to fully adapt to pressure overload following nTAC on postnatal day 1. In contrast, when nTAC is applied in the non-regenerative phase (at postnatal day 7), it is associated with a maladaptive response similar to that seen when transverse aortic constriction (TAC) is applied to adult mice. Once a user is experienced in nTAC surgery, the procedure can be completed in less than 10 min per mouse. We anticipate that this model will facilitate the discovery of therapeutic targets to treat patients or prevent pressure overload-induced cardiac failure in the future.

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Fig. 1: Surgery setup.
Fig. 2: Schematic and microscopic views of the surgical procedures.
Fig. 3: Doppler flow velocity measurement.
Fig. 4: Echocardiography of 7-day-old mice.
Fig. 5: Representative whole-heart images following nTAC and sham surgeries.
Fig. 6: Pressure overload reduces cardiac function in 7-day-old mice but not 1-day-old mice.

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Data availability

No new datasets were generated or analyzed during the current study. A data source file containing the data shown in Fig. 6 (all previously published in ref. 17) is provided as Source Data.

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Acknowledgements

The establishment of the nTAC model was supported by the Deutsche Forschungsgemeinschaft through the Cluster of Excellence REBIRTH (EXC62/3), the Heisenberg Program (HE3658/6-1 and HE3658/6-2), and a research grant HE 3658/11-1. The schematic images used in the figures are from Servier Medical Art (https://smart.servier.com/).

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Authors and Affiliations

  1. Department of Cardiovascular Physiology, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Mona Malek Mohammadi, Aya Abouissa & Joerg Heineke

  2. German Center for Cardiovascular Research (DZHK), partner site Heidelberg, Mannheim, Germany

    Mona Malek Mohammadi, Aya Abouissa & Joerg Heineke

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  1. Mona Malek Mohammadi
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  2. Aya Abouissa
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Contributions

M.M.M. and J.H. designed the study, planned all the experiments, and analyzed the data. M.M.M. established the methods and performed the surgeries and experiments. A.A. captured the images. M.M.M. and J.H. wrote the manuscript. J.H. supervised the study. All authors read and approved the manuscript.

Corresponding authors

Correspondence to Mona Malek Mohammadi or Joerg Heineke.

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The authors declare no competing interests.

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Peer review information Nature Protocols thanks Robert Blanton and Yingjie Chen for their contribution to the peer review of this work.

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Related links

Key reference using this protocol

Malek Mohammadi, M. et al. JCI Insight 4, e128336 (2019): https://doi.org/10.1172/jci.insight.128336

Key data used in this protocol

Malek Mohammadi, M. et al. JCI Insight 4, e128336 (2019): https://doi.org/10.1172/jci.insight.128336

Supplementary information

Supplementary Information

Supplementary Materials and Methods.

Reporting Summary

Supplementary Video 1

Video demonstrating the nTAC procedure

Source data

Source Data Fig. 6

Source data.

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Malek Mohammadi, M., Abouissa, A. & Heineke, J. A surgical mouse model of neonatal pressure overload by transverse aortic constriction. Nat Protoc 16, 775–790 (2021). https://doi.org/10.1038/s41596-020-00434-9

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