Cardioprotection in acute myocardial infarction

Fabrice Prunier, PU-PH

FaPrunier@chu-angers.fr

Team members

Preclinical team 

Fabrice Prunier, M.D. , Ph.D.,  PU-PH

Sophie Tamareille, Ph.D.,  Engineer UA

Lucie Lebeau, Engineer UA

Aglae Herbreteau, Technician UA

Louwana Allawa, Ph.D. student

Xavier Dieux, Ph.D. student

Tom Boursier, Master 2 student

Clinical team

Fabrice Prunier, M.D. , Ph.D.,  PU-PH

Alain Furber, M.D. , Ph.D.,  PU-PH

Loic Bière, M.D. , Ph.D.,  MCU-PH

Jérémy Rautureau, Clinical trial engineer

Thiébaud Boucher, Clinical trial engineer

Myocardial infarction is a leading cause of death worldwide.  Although prompt reperfusion is crucial to reduce the infarct size and improve survival, it can paradoxically induce injury itself, leading to functional and metabolic disruptions of the heart as well as morphological changes. Cardioprotective strategies are developed to reduce the impact of reperfusion injury in experimental models and in randomized clinical trials.

Our aim is to investigate, using experimental and clinical approaches, the molecular and cellular mechanisms underlying myocardial ischemia/reperfusion injury and left ventricular remodeling after myocardial infarction.

Isolated mouse ventricular cardiomyocytes.

Technical platform : Cardiac function in vivo, ex vivo, in vitro

In vivo exploration

• Echocardiography Doppler (Vivid 7, GE Healthcare)
• Implantable telemetry ECG (DSI)
• Hemodynamics (Millar pressure catheter)
• Myocardial infarction models (mice and rats): myocardial ischemia/reperfusion, permanent coronary artery occlusion

Ex vivo cardiac function

• Langendorff isolated perfused heart (mice and rats) with monitoring of hemodynamic parameters (EMKA Technologies, ADInstruments)

In vitro

• Hypoxia/reoxygenation on isolated adult and neonatal cardiomyocytes (rat, mice) and H9C2 cell line

Selected recent publications

Preclinical publications

Guillou S, Beaumont J, Tamareille S, Giraud S, Mirebeau-Prunier D, Prunier F, Macchi L. Direct Rivaroxaban-Induced Factor Xa Inhibition Proves to be Cardioprotective in Rats. Shock 2020;53:730-736.

Bakhta O, Pascaud A, Dieu X, Beaumont J, Kouassi Nzoughet J, Kamel R, Croyal M, Tamareille S, Simard G, Chao de la Barca JM, Reynier P, Prunier F, Mirebeau-Prunier D. Tryptophane-kynurenine pathway in the remote ischemic conditioning mechanism. Basic Res Cardiol. 2020;115:13.

Behaghel V, Tamareille S, Rabant M, Mirebeau-Prunier D, Bière L, Macchi L, Prunier F. Remote Ischemic Conditioning in a Model of Severe Renal Ischemia-Reperfusion Injury. Shock. 2019;51:795-799.

Bakhta O, Blanchard S, Guihot AL, Tamareille S, Mirebeau-Prunier D, Jeannin P, Prunier F. Cardioprotective Role of Colchicine Against Inflammatory Injury in a Rat Model of Acute Myocardial Infarction. J Cardiovasc Pharmacol Ther. 2018;23:446-455.

Le Page S, Niro M, Fauconnier J, Cellier L, Tamareille S, Gharib A, Chevrollier A, Loufrani L, Grenier C, Kamel R, Sarzi E, Lacampagne A, Ovize M, Henrion D, Reynier P, Lenaers G, Mirebeau-Prunier D, Prunier F. Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model. PLoS One. 2016;11:e0164066

Chao de la Barca JM, Bakhta O, Kalakech H, Simard G, Tamareille S, Catros V, Callebert J, Gadras C, Tessier L, Reynier P, Prunier F, Mirebeau-Prunier D. Metabolic Signature of Remote Ischemic Preconditioning Involving a Cocktail of Amino Acids and Biogenic Amines. J Am Heart Assoc. 2016;5:e003891.

Kauffenstein G, Tamareille S, Prunier F, Roy C, Ayer A, Toutain B, Billaud M, Isakson BE, Grimaud L, Loufrani L, Rousseau P, Abraham P, Procaccio V, Monyer H, de Wit C, Boeynaems JM, Robaye B, Kwak BR, Henrion D. Central Role of P2Y6 UDP Receptor in Arteriolar Myogenic Tone. Arterioscler Thromb Vasc Biol. 2016;36:1598-606.

Guillou S, Tamareille S, Giraud S, Poitevin G, Prunier-Mirebeau D, Nguyen P, Prunier F, Macchi L.
Fondaparinux upregulates thrombomodulin and the endothelial protein C receptor during early-stage reperfusion in a rat model of myocardial infarction. Thromb Res. 2016;141:98-103.

Cellier L, Tamareille S, Kalakech H, Guillou S, Lenaers G, Prunier F, Mirebeau-Prunier D. REMOTE ISCHEMIC CONDITIONING INFLUENCES MITOCHONDRIAL DYNAMICS.Shock. 2016;45(2):192-7.

Clinical publications

Mesnier J, Cottin Y, Coste P, Ferrari E, Schiele F, Lemesle G, Thuaire C, Angoulvant D, Cayla G, Bouleti C, Gallet de Saint Aurin R, Goube P, Lhermusier T, Dillinger JG, Paganelli F, Saib A, Prunier F, Vanzetto G, Dubreuil O, Puymirat E, Boccara F, Eltchaninoff H, Cachanado M, Rousseau A, Drouet E, Steg PG, Simon T, Danchin N. Hospital admissions for acute myocardial infarction before and after lockdown according to regional prevalence of COVID-19 and patient profile in France: a registry study. Lancet Public Health. 2020;5:e536-e542

Hernandez-Resendiz S, Prunier F, Girao H, Dorn G, Hausenloy DJ; EU-CARDIOPROTECTION COST Action (CA16225). Targeting mitochondrial fusion and fission proteins for cardioprotection. J Cell Mol Med. 2020 Jun;24:6571-6585.

Ingremeau D, Grall S, Valliet F, Desprets L, Prunier F, Furber A, Bière L. Prognostic impact of body mass index on in-hospital bleeding complications after ST-segment elevation myocardial infarction. World J Cardiol. 2020;12:44-54.

Grall S, Bouteau R, Hamel JF, Garcia G, Delagarde H, Willoteaux S, Dubus V, Prunier F, Furber A, Bière L. Left Ventricular Remodeling in ST-Segment Elevation Myocardial Infarction Patients With Depressed Left Ventricular Ejection Fraction After Cardiac Rehabilitation. JACC Cardiovasc Imaging. 2019;12:938-939.

Roubille F, Macia JC, Ivanes F, Angoulvant D, Mateus V, Belle L, Elbaz M, Morel O, Furber A, Bière L, Prunier F. Effects of remote ischemic conditioning on kidney injury in at-risk patients undergoing elective coronary angiography (PREPARE study): a multicenter, randomized clinical trial. Sci Rep. 2019;9:11985.

Gourronc Y, Grall S, Ingremeau D, Desprets L, Prunier F, Furber A, Bière L. De novo atrial fibrillation as an independent prognostic marker after ST-segment elevation myocardial infarction: Results from the RIMA registry. J Cardiol. 2019;74:123-129.

Madonna R, Van Laake LW, Botker HE, Davidson SM, De Caterina R, Engel FB, Eschenhagen T, Fernandez-Aviles F, Hausenloy DJ, Hulot JS, Lecour S, Leor J, Menasché P, Pesce M, Perrino C, Prunier F, Van Linthout S, Ytrehus K, Zimmermann WH, Ferdinandy P, Sluijter JPG. ESC Working Group on Cellular Biology of the Heart: position paper for Cardiovascular Research: tissue engineering strategies combined with cell therapies for cardiac repair in ischaemic heart disease and heart failure. Cardiovasc Res. 2019;115:488-500.

Garcia G, Chao de la Barca JM, Mirebeau-Prunier D, Reynier P, Furber A, Prunier F, Bière L. Metabolomic Approach in STEMI-Patients Undergoing Left Ventricular Remodeling. Int J Mol Sci. 2019;20(2). pii: E289.

Bière L, Garcia G, Guillou S, Larcher F, Furber A, Willoteaux S, Mirebeau-Prunier D, Prunier F. ST2 as a predictor of late ventricular remodeling after myocardial infarction. Int J Cardiol. 2018;259:40-42.

Bière L, Mezdad TH, Dupuis JM, Vervueren L, Rakotonirina H, Prunier F, Furber A. Long-term prognostic significance of right bundle-branch morphology ventricular ectopy induced during stress test in patients with intermediate to high probability of coronary artery disease. Europace. 2018;20:528-534.

Bonin M, Mewton N, Roubille F, Morel O, Cayla G, Angoulvant D, Elbaz M, Claeys MJ, Garcia-Dorado D, Giraud C, Rioufol G, Jossan C, Ovize M, Guerin P; CIRCUS Study Investigators. Effect and Safety of Morphine Use in Acute Anterior ST-Segment Elevation Myocardial Infarction. J Am Heart Assoc. 2018;7.

Sluijter JPG, Davidson SM, Boulanger CM, Buzás EI, de Kleijn DPV, Engel FB, Giricz Z, Hausenloy DJ, Kishore R, Lecour S, Leor J, Madonna R, Perrino C, Prunier F, Sahoo S, Schiffelers RM, Schulz R, Van Laake LW, Ytrehus K, Ferdinandy P. Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res. 2018;114:19-34.

Bière L, Behaghel V, Mateus V, Assunção A Jr, Gräni C, Ouerghi K, Grall S, Willoteaux S, Prunier F, Kwong R, Furber A. Relation of Quantity of Subepicardial Adipose Tissue to Infarct Size in Patients With ST-Elevation Myocardial Infarction. Am J Cardiol. 2017;119:1972-1978.

Pinaud F, Corbeau JJ, Baufreton C, Binuani JP, De Brux JL, Fouquet O, Angoulvant D, Furber A, Prunier F. Remote ischemic preconditioning in aortic valve surgery: Results of a randomized controlled study. J Cardiol. 2016 Jan;67:36-41.

Collaborations

Institute of Experimental and Clinical Research, University of Louvain, Belgium  (Luc Bertrand)

INSERM U1060 CarMeN, Lyon (Delphine Baetz)

INSERM U1232 CRCINA Equipe 07, Angers (Pascale Jeannin, Yves Delneste)

Hôpital Louis Pradel, Lyon (Thomas Bochaton)

INSERM 1082 IRTOMIT, Poitiers (Laurent Macchi)

INSERM U955-IMR, Créteil (Bijan Ghaleh)

CHRU Tours (Denis Angoulvant)

Center for Interdisciplinary Research in Biology (CIRB), Collège de France, Paris (Stéphane Germain)