CARDIOPROTECTION, PHYSIOPATHOLOGY OF HEART RYTHM AND ISCHEMIA
Department : Physiology and Cancer
Research subject
Research theme: Cardiovascular diseases, including myocardial infarction and arrhythmias remain the leading cause of death in the world in 2019. By 2030, nearly 23.6 million people will die from cardiovascular disease, so it is essential to maintain our efforts in the field of cardioprotection.
Two parameters are paramount to preserve the cardiac performance: (i) the heart pacemaker activity activity, which generates the cardiac impulse and controls the ventricular rhythm, and (ii) the contraction efficiency of the myocardium. In this context, research projects of the team focus on the study of the cellular mechanisms involved, on the one hand, in the control of pacemaker activity and, on the other hand, in the processes of cell death leading to injury after myocardial infarction. The objectives of the team are to develop cardioprotective strategies to normalize heart rate and to inhibit cardiac cell apoptosis, in order to prevent ventricular remodeling leading to heart failure.
Strategy and techniques: The team uses mouse models of cardiac pathology such as transgenic mice with sick sinus syndrome, brady- or tachyarrhythmias. For the model of myocardial infarction, the reversible coronary ligation surgical model is used to best mimic the clinical context of myocardial ischemia-reperfusion. The technical platform of the team consists of all the devices for non-invasive pre-clinical monitoring with telemetric ECG recordings and echocardiography. Ex vivo experiments with isolated hearts (Langendorff) and in vitro recordings of contraction and electrical activity (DMT, patch-clamp, ..) are also performed to study the mechanistic aspects.
The team is part of the labex ICST (Ion Channel Science and Therapeutics and of the RegenHab FHU.
Team
Major publications
- Mesirca, P., Alig, J., Torrente, A.G., Muller, J.C., 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, M.E. (2014a). Cardiac arrhythmia induced by genetic silencing of 'funny' (f) channels is rescued by GIRK4 inactivation. Nat Commun 5, 4664.
- Mesirca, P., Bidaud, I., Briec, F., Evain, S., Torrente, A.G., Le Quang, K., Leoni, A.L., Baudot, M., Marger, L., Chung You Chong, A., Nargeot, J., Striessnig, J., Wickman, K., Charpentier, F., and Mangoni, M.E. (2016a). G protein-gated IKACh channels as therapeutic targets for treatment of sick sinus syndrome and heart block. Proc Natl Acad Sci U S A 113, E932-941.
- Torrente, A.G., Mesirca, P., Neco, P., Rizzetto, R., Dubel, S., Barrere, C., Sinegger-Brauns, M., Striessnig, J., Richard, S., Nargeot, J., Gomez, A.M., and Mangoni, M.E. (2016). L-type Cav1.3 channels regulate ryanodine receptor-dependent Ca2+ release during sino-atrial node pacemaker activity. Cardiovasc Res 109, 451-461.
- Toyoda, F., Mesirca, P., Dubel, S., Ding, W.G., Striessnig, J., Mangoni, M.E., and Matsuura, H. (2017). CaV1.3 L-type Ca2+ channel contributes to the heartbeat by generating a dihydropyridine-sensitive persistent Na+ current. Sci Rep 7, 7869.
- Vincent, A., Covinhes, A., Barrere, C., Gallot, L., Thoumala, S., Piot, C., Heurteaux, C., Lazdunski, M., Nargeot, J., and Barrere-Lemaire, S. (2017a). Acute and long-term cardioprotective effects of the Traditional Chinese Medicine MLC901 against myocardial ischemia-reperfusion injury in mice. Sci Rep 7, 14701.
- Vincent, A., Sportouch, C., Covinhes, A., Barrere, C., Gallot, L., Delgado-Betancourt, V., Lattuca, B., Solecki, K., Boisguerin, P., Piot, C., Nargeot, J., and Barrere-Lemaire, S. (2017b). Cardiac mGluR1 metabotropic receptors in cardioprotection. Cardiovasc Res 113, 644-655.
- Saponaro, A., Cantini, F., Porro, A., Bucchi, A., DiFrancesco, D., Maione, V., Donadoni, C., Introini, B., Mesirca, P., Mangoni, M.E., Thiel, G., Banci, L., Santoro, B., and Moroni, A. (2018). A synthetic peptide that prevents cAMP regulation in mammalian hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Elife 7.
- Boisguerin, P., Covinhes, C., Gallot, L., Barrere, C., Vincent, A., Busson, M., Piot, C., Nargeot, J., Lebleu, B., and Barrere-Lemaire, S. (2019). A novel therapeutic peptide targeting myocardial reperfusion injury. Cardiovasc Res 2019 May 30. pii: cvz145. doi: 10.1093/cvr/cvz145. [Epub ahead of print]