Identifying treatment and biomarkers in heart failure

Benjamin Lauzier, Bertrand Rozec, Marja Steeman, Chantal Gauthier, Michel De Waard

The objective of our group is to improve the understanding of heart failure in acute and chronic features. By developing new animal models and approaches in acute cardiac decompensation or in chronic heart failure such as heart failure with preserved ejection fraction.
 

• Acute heart failure: Secretome

By using various model (sepsis in rat, extracorporeal circulation in patient) we aim at decipher the role of secretome in cardiovascular failure during shock situation. Thanks to mass spectrometry approaches we expect to determine new biomarkers and therapeutic targets to improve patient outcome.
 

• Chronic heart failure: Preclinical development

Thanks to a collaboration with SANOFI we have characterized a new model of Chronic heart failure with preserved ejection fraction and we have been working with a group of researcher from france (JS Hulot, Paris, MA Renault, Bordeaux, P Mulder, Rouen) and company (Sanofi) to improve the understanding of heart failure with preserved ejection fraction. Heart failure with the preserved ejection fraction (HFpEF), which currently accounts for 50% of all HF patients, has become a major clinical problem without effective treatment. Using our HFpEF animal model (beta3-receptor-overexpressing rat) and blood of patients suffering from HFpEF (cohort and biocollection under construction), our aims are to identify biomarkers and molecular targets relevant to this major cardiovascular burden.

Overexpression of endothelial β3 -adrenergic receptor induces diastolic dysfunction in rats.
Dhot J, Ferron M, Prat V, Persello A, Roul D, Stévant D, Guijarro D, Piriou N, Aillerie V, Erraud A, Toumaniantz G, Erfanian M, Tesse A, Grabherr A, Tesson L, Menoret S, Anegon I, Trochu J-N, Steenman M, De Waard M, Rozec B, Lauzier B, Gauthier C.
ESC Heart Fail 2020

Human Heart Failure with preserved ejection fraction versus feline cardiomyopathy: what can we learn from both veterinary and human medicine?
V Prat, B Rozec, C Gauthier, B Lauzier.
Heart Fail rev. Aout 2017. 

Acute detachment of hexokinase II from mitochondria modestly increases oxygen consumption of the intact mouse heart.
R Nederlof, S Denis, B Lauzier, C Des Rosiers, M Laakso, J Hagen, C Argmann, R Wanders, RH Houtkooper, M.W. Hollmann, SM Houten, CJ Zuurbier.
Metabolism. Juillet 2017. 

Ivabradine and metoprolol differentially affect cardiac glucose metabolism despite similar heart rate reduction in a mouse model of dyslipidemia.
Vaillant F, Lauzier B, Ruiz M, Shi Y, Lachance D, Rivard ME, Bolduc V, Thorin E, Tardif JC, Des Rosiers C.
Am J Physiol Heart Circ Physiol. 2016. 

PCSK9 Induces CD36 Degradation and Affects Long-Chain Fatty Acid Uptake and Triglyceride Metabolism in Adipocytes and in Mouse Liver.
Demers A, Samami S, Lauzier B, Des Rosiers C, Sock ET, Ong H, Mayer G.
Arterioscler Thromb Vasc Biol. 2015 Oct 22. 

Funding

This programme has been financed by :
 

• Agence Nationale de la Recherche
• Fédération Française de Cardiologie
• Fédération pour la Recherche Médicale
• Sanofi
• Genavie
• Sauve Ton Cœur