Acute stress induces long-term metabolic, functional, and structural remodeling of the heart

Thulaciga Yoganathan (), Mailyn Perez-Liva, Daniel Balvay, Morgane Gall, Alice Lallemand, Anais Certain, Gwennhael Autret, Yasmine Mokrani, François Guillonneau, Johanna Bruce, Vincent Nguyen, Umit Gencer, Alain Schmitt, Franck Lager, Thomas Guilbert, Patrick Bruneval, Jose Vilar, Nawal Maissa, Elie Mousseaux, Thomas Viel, Gilles Renault, Nadjia Kachenoura and Bertrand Tavitian ()
Additional contact information
Thulaciga Yoganathan: Université Paris Cité, Inserm, PARCC
Mailyn Perez-Liva: Université Paris Cité, Inserm, PARCC
Daniel Balvay: Université Paris Cité, Inserm, PARCC
Morgane Gall: Institut Cochin, INSERM, CNRS
Alice Lallemand: Université Paris Cité, Inserm, PARCC
Anais Certain: Université Paris Cité, Inserm, PARCC
Gwennhael Autret: Université Paris Cité, Inserm, PARCC
Yasmine Mokrani: Université Paris Cité, Inserm, PARCC
François Guillonneau: Institut de Cancérologie de l’Ouest, CNRS UMR6075 INSERM U1307
Johanna Bruce: Institut Cochin, INSERM, CNRS
Vincent Nguyen: Sorbonne Université, Laboratoire d’Imagerie Biomédicale, Inserm, CNRS
Umit Gencer: AP-HP, hôpital européen Georges Pompidou
Alain Schmitt: Institut Cochin, INSERM, CNRS
Franck Lager: Institut Cochin, Inserm-CNRS
Thomas Guilbert: Institut Cochin, Inserm, CNRS
Patrick Bruneval: Université Paris Cité, Inserm, PARCC
Jose Vilar: Université Paris Cité, Inserm, PARCC
Nawal Maissa: Université Paris Cité, Inserm, PARCC
Elie Mousseaux: AP-HP, hôpital européen Georges Pompidou
Thomas Viel: Université Paris Cité, Inserm, PARCC
Gilles Renault: Institut Cochin, Inserm-CNRS
Nadjia Kachenoura: Sorbonne Université, Laboratoire d’Imagerie Biomédicale, Inserm, CNRS
Bertrand Tavitian: Université Paris Cité, Inserm, PARCC

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Takotsubo cardiomyopathy is a stress-induced cardiovascular disease with symptoms comparable to those of an acute coronary syndrome but without coronary obstruction. Takotsubo was initially considered spontaneously reversible, but epidemiological studies revealed significant long-term morbidity and mortality, the reason for which is unknown. Here, we show in a female rodent model that a single pharmacological challenge creates a stress-induced cardiomyopathy similar to Takotsubo. The acute response involves changes in blood and tissue biomarkers and in cardiac in vivo imaging acquired with ultrasound, magnetic resonance and positron emission tomography. Longitudinal follow up using in vivo imaging, histochemistry, protein and proteomics analyses evidences a continued metabolic reprogramming of the heart towards metabolic malfunction, eventually leading to irreversible damage in cardiac function and structure. The results combat the supposed reversibility of Takotsubo, point to dysregulation of glucose metabolic pathways as a main cause of long-term cardiac disease and support early therapeutic management of Takotsubo.

Date: 2023
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DOI: 10.1038/s41467-023-39590-3

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