Acute stress induces long-term metabolic, functional, and structural remodeling of the heart
Thulaciga Yoganathan, Mailyn Pérez-Liva, Daniel Balvay, Morgane Le Gall, A Lallemand, Anaïs Certain, Gwennhaël Autret, Yasmine Mokrani, François Guillonneau, Johanna Bruce, Vincent Nguyen, Umit Gencer, Alain Schmitt, Franck Lager, Thomas Guilbert, Patrick Bruneval, José Vilar, Nawal Maïssa, Élie Mousseaux, Thomas Viel, Gilles Renault, Nadjia Kachenoura, Bertrand Tavitian
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.