CARDIOVASCULAR AND PHYSIOPATHOLOGY
Department : Physiology - Research axis : Biology of ion channels

 

Research subject

Cardiovascular disease constitutes the first cause of mortality worldwide. We can estimate that in 2030 about 23.6 millions people will decease of cardiovascular disease. It is thus very important to constantly develop new therapeutic strategies. The cardiac performance is determined by the properties of pacemaker activity as well myocardial contractility. In humans, the heart rate is an important prognostic factor of morbidity and mortality in cardiac disease. Our research team focuses on the cellular mechanisms underlying the genesis and control of cardiac pacemaking and to elucidate the cellular and molecular mechanisms underlying myocytes survival or death during cardiac ischemic processes. Our objective is to indicate new molecular targets for controlling heart rate and protect the myocardium during ischemic heart disease.
In the past, we have introduced the use of genetically-modified mice in the study of pacemaker activity and described the role of Cav1.3, Cav3.1, HCN4 channels and more recently TRPM7 and Girk4 channels in cardiac automaticity and impulse conduction in mice and humans. Our work demonstrated that cardiac pacemaking is a complex phenomenon involving both ion channels and proteins involved in intracellular calcium release. All these pacemaker mechanisms are potentially involved in congenital diseases of heart automaticity. Also, these molecular entities could constitute new targets for controlling heart rate in cardiac disease.

Our group now studies the complex interactions between ion channels of the plasma membrane and intracellular signalling pathways underlying pacemaking. The infarct size is another important prognostic factor of mortality and constitutes, together with stroke, the principal cause of cardiovascular mortality. By associating protocols inducing cardioprotection on animal models and in clinical trials we now aim to identify new candidate genes and pharmacological tools to antagonize cell apoptosis underling ischemia-reperfusion injury, thereby reducing infarct size.

The team is part of the labex ICST (Ion Channel Science and Therapeutics) : http://www.labex-icst.fr/fr

 

 

Team

Team leader

Stephanie Barrere
DR2, CNRS


  IGF Sud 126

  04 34 35 92 46

 

Matteo Mangoni
DR2, CNRS


  IGF Sud 126

  04 34 35 92 44

 

Staff

Christian Barrere
IE, CNRS


  IGF Sud 121

  04 34 35 92 45

 

Matthias Baudot
Doctorant(e), CNRS


  IGF Sud 126

  04 34 35 92 46

 

Isabelle Bidaud
IE, Inserm


  IGF Sud 121

  04 34 35 92 45

 

Antony Chung You Chong
Doctorant(e), CNRS


  IGF Sud 121

  04 34 35 92 45

 

Lucile Fossier
Master 2, UM


  IGF Sud 126

  04 34 35 96 80

 

Laura Gallot
AI, CNRS


  IGF Sud 104

  04 34 35 92 47

 

Pietro Mesirca
CRCN, Inserm


  IGF Sud 126

  04 34 35 92 46

 

Joel Nargeot
DRE, CNRS


  IGF Sud 122

  04 34 35 92 44

 

Christophe Piot
PU, Clinique du Millénaire


  IGF Sud 126

  04 34 35 92 46

 

Jantira Sanit
Accueil scientifique, CNRS


  IGF Sud 126

  04 34 35 92 46

 

Charlotte Sarre
Doctorant(e), Inserm


  IGF Sud 126

  04 34 35 92 46

 

Angelo Torrente
Post-doctorant(e), UM


  IGF Sud 126

  04 34 35 92 46

 

Anne Vincent
MCF, UM


  IGF Sud 126

  04 34 35 92 46

 


Major publications

  • Mesirca P, Alig J, Torrente AG, JC Müller Marger L, , Rollin A, Marquilly C, Vincent A, Dubel S, Bidaud I, Fernandez A, Seniuk A, Engeland B, Singh J, Miquerol L, Ehmke H, Eschenhagen T, Nargeot J, Wickman K, Isbrandt D and Mangoni ME. (2014) Cardiac arrhythmia induced by genetic silencing of "funny" (f)-channels is rescued by Girk4 inactivation. NATURE Communications 2014 Aug 21;5:4664. doi: 10.1038/ncomms5664.
  • Sah R, Mesirca P, Mason X, Gibson W, Bates-Withers C, Van den Boogert M, Chandhuri D, Pu W, Mangoni ME, and Clapham DE. The timing of myocardial Trpm7 deletion during cardiogenesis variably disrupts adult ventricular function, conduction and repolarization. 2013 Circulation. 128(2):101-14.
  • Neco P, Torrente A, Mesirca P, Zorio E, Liu N, Priori SG, Napolitano C, Richard S, Benitah JP, Mangoni ME, Gómez AM (2012) Paradoxical Effect of Increased Diastolic Ca2+ Release and Decreased Sinoatrial Node Activity in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia. 2012 Circulation. 126(4):392-401.
  • Roubille F., Franck-Miclo A., Covinhes A., Lafont C., Cransac F., Combes S., Vincent A., Fontanaud P., Sportouch-Dukhan C., Redt-Clouet C., Nargeot J., Piot C., Barrère-Lemaire S. Delayed postconditioning in the mouse heart in vivo. Circulation. 2011 20;124(12):1330-6. Epub 2011 Aug 29. (related editorial: Opie LH, Lecour S. Delayed postconditioning: cardioprotection at the limit? Circulation. 2011 Sep 20;124(12):1315-8) .
  • Vincent A, Gahide G, Sportouch-Dukhan C, Covinhes A, Franck-Miclo A, Roubille F, Barrère C, Adda J, Dantec C, Redt-Clouet C, Piot C, Nargeot J, Barrère-Lemaire S. Downregulation of the transcription factor ZAC1 upon PreC and PostC protects against ischemia-reperfusion in the mouse myocardium. Cardiovasc Res. 2012 May 1;94(2):351-8. Epub 2011 Nov 21. (Related editorial: Piper HM and Garcia-Dorado D. Reducing the impact of myocardial ischaemia/reperfusion injury. Cardiovasc Res (2012) 94 (2): 165-167).
 

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