(February 23, 2021) WEBINAR: Neonatal model of transverse aortic constriction (nTAC) to induce pressure overload

Overview:

Learning objectives:

• How to perform neonatal model of transverse aortic constriction (nTAC) to induce pressure overload in neonatal mice?
• How to confirm the surgery using Doppler Flow Velocity measurements?
• How to confirm the surgery and assess the outcome using echocardiography?
• What is the outcome of induced pressure overload at P1 vs P7?
• What are the challenges and pitfalls to avoid?
• Troubleshooting

Cardiac disease is the main cause of death worldwide. Insufficient regeneration of the adult mammalian heart owing to the lack of cardiomyocyte proliferation and scarce therapeutic options for patients with advanced cardiac disease are major drivers of cardiac morbidity and mortality. Cardiac regeneration through cardiomyocyte proliferation occurs only in early postnatal mice but is lost shortly after birth when cardiomyocytes withdraw from the cell cycle ^1,2.

Dr. Malek Mohammadi has recently established a neonatal model of transverse aortic constriction, to induce pressure overload in neonatal mice in the regenerative phase (postnatal day 1(P1) or in non-regenrative phase (P7). Her lab has demonstrated that neonatal mice at postnatal day 1 (P1) have the ability to adapt to pressure overload, but this ability is lost by P7³. This adaptive mechanism in the regeneration phase (P1) is associated with preserved cardiac function, augmented cardiomyocyte proliferation and increased angiogenesis. Only seven days of pressure overload in the non-regenerative phase (P7), however, is associated with fibrosis in the heart and reduced cardiac function^3,4. Thus, this fundamentally different response of the postnatal mouse heart to a pathological stimulus provides a model to explore the endogenous mechanism(s) underlying the adaptive and maladaptive response of the mammalian heart.

In this webinar, Dr. Malek Mohammadi provided an overview of the surgical protocol of neonatal model of transverse aortic constriction (nTAC) including postsurgical monitoring and ways to confirm the surgery using Doppler flow velocity measurements and echocardiography.

Furthermore, she discussed troubleshooting of some common problems that you might face during the surgery, and employing flow velocity and echocardiography.

The full protocol including video of the surgery is published at Nature Protocols and is available online: Malek Mohammadi, M., Abouissa, A. & Heineke, J. A surgical mouse model of neonatal pressure overload by transverse aortic constriction. Nat Protoc (2020). https://doi.org/10.1038/s41596-020-00434-9

1. Porrello, E. R. et al. Transient regenerative potential of the neonatal mouse heart. Science 331, 1078-1080, doi:10.1126/science.1200708 (2011).
2. Malek Mohammadi, M. et al. The transcription factor GATA4 promotes myocardial regeneration in neonatal mice. EMBO Mol Med 9, 265-279, doi:10.15252/emmm.201606602 (2017).
3. Malek Mohammadi, M. et al. Induction of cardiomyocyte proliferation and angiogenesis protects neonatal mice from pressure overload-associated maladaptation. JCI Insight 5, doi:10.1172/jci.insight.128336 (2019).
4. Malek Mohammadi M., A. A., Heineke J. A Surgical Mouse Model of Neonatal Pressure Overload by Transverse Aortic Constriction. Nature Protocols (2020).

Publication

Malek Mohammadi, M., Abouissa, A. & Heineke, J. A surgical mouse model of neonatal pressure overload by transverse aortic constriction. Nat Protoc (2020).