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Pharmacological strategies and experimental therapeutics for myocardial ischemia and heart failure

Contacts

Bijan Ghaleh-Marzban Head Bijan Ghaleh-Marzban

Tél.: +33-(0)1 43 96 73 85
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The team investigates the pathophysiology and pharmacology of coronary disease and cardiac failure. Our facilities are closely linked to Henri Mondor hospital (PHYDES department “Ageing-Thorax, Vessel, Blood” DHU) and involve two integrated and nearly located labs in the National Veterinary School of Maisons-Alfort (ENVA) and Creteil Medical School (Université Paris Est Créteil). For 2015-2019, the objectives are to further investigate the physiopathological mechanisms leading to left ventricular (LV) dysfunction and to develop original and innovative pharmacological strategies to prevent or reduce LV dysfunctions.

 

Our goal is to establish proofs of concepts

1) for new pharmacological/technological developments and

2) to promote translational clinical research.

 

Our first aim is to protect the heart and to reduce infarct size by targeting the mitochondrial cholesterol translocation with TSPO ligands or by using new molecules targeting the mitochondrial cyclophilin D. Protection of the coronary vasculature with angiopoietin-like 4 will be also a main topic of the team as well as impact of comorbidities such as obesity.

 

Our second aim is to evaluate the consequences of cardiac arrest by deciphering the benefits afforded by hypothermia with total liquid ventilation and developing specific liquid ventilators for clinical use.

 

Our third aim is to study LV dysfunction and its calcium-related mechanism in an original hypertensive pig model that develops diastolic dysfunction and ultimately heart failure with preserved ejection fraction.

 

All these objectives also include clinical translation with ongoing and new clinical trials. In addition, within ENVA, our programs will be extended to animals with spontaneous and/or genetic diseases (e.g., Golden Retriever Muscular Dystrophy dogs mimicking human Duchenne myopathy).

 

Finally, the team will remain highly involved in student training (doctoral school “Sciences de la Vie et de la Santé”).


 

Selected publications

Kohlhauer M1, Lidouren F, Remy-Jouet I, Mongardon N, Adam C, Bruneval P, Hocini H, Levy Y, Blengio F, Carli P, Vivien B, Ricard JD, Micheau P, Walti H, Nadeau M, Robert R, Richard V, Mulder P, Maresca D, Demené C, Pernot M, Tanter M, Ghaleh B, Berdeaux A, Tissier R. Hypothermic Total Liquid Ventilation Is Highly Protective Through Cerebral Hemodynamic Preservation and Sepsis-Like Mitigation After Asphyxial Cardiac Arrest.

Crit Care Med. 2015 Jun 23. [Epub ahead of print]

Su JB, Cazorla O, Blot S, Blanchard-Gutton N, Ait Mou Y, Barthelemy I, Sambin L, Sampedrano CC, Gouni V, Unterfinger Y, Aguilar P, Thibaud JL, Bize A, Pouchelon JL, Dabire H, Ghaleh B, Berdeaux A, Chetboul V, Lacampagne A, Hittinger L. Bradykinin restores left ventricular function, sarcomeric protein phosphorylation and e/nNOs levels in dogs with Duchenne muscular dystrophy cardiomyopathy.

Cardiovasc Res. 2012; 95:86-96. (IF 5.9)

Rienzo M, Bizé A, Pongas D, Michineau S, Melka J, Chan HL, Sambin L, Su JB, Dubois-Randé JL, Hittinger L, Berdeaux A, Ghaleh B. Impaired left ventricular function in the presence of preserved ejection in chronic hypertensive conscious pigs.

Basic Res Cardiol. 2012; 107: 298. (IF 5.9)

Galaup A, Gomez E, Souktani R, Durand M, Cazes A, Monnot C, Teillon J, Le Jan S, Bouleti C, Briois G, Philippe J, Pons S, Martin V, Assaly R, Bonnin P, Ratajczak P, Janin A, Thurston G, Valenzuela DM, Murphy AJ, Yancopoulos GD, Tissier R, Berdeaux A, Ghaleh B, Germain S. Protection against myocardial infarction and no-reflow through preservation of vascular integrity by angiopoietin-like 4.

Circulation. 2012; 125: 140-9. (IF 15.2)

Chenoune M, Lidouren F, Adam C, Pons S, Darbera L, Bruneval P, Ghaleh B, Zini R, Dubois-Rande JL, Carli P, Vivien B, Ricard JD, Berdeaux A, Tissier R. Ultrafast and whole-body cooling with total liquid ventilation induces favorable neurological and cardiac outcomes after cardiac arrest in rabbits.

Circulation. 2011; 124: 901-11, 1-7. (IF 15.2).

Couvreur N, Tissier R, Pons S, Chetboul V, Gouni V, Bruneval P, Mandet C, Pouchelon JL, Berdeaux A, Ghaleh B. Chronic heart rate reduction with ivabradine improves systolic function of the reperfused heart through a dual mechanism involving a direct mechanical effect and a long-term increase in FKBP12/12.6 expression.

Eur Heart J. 2010; 31: 1529-37. (IF 14.0).