par- 26 juin 2012
Physiopathologie cardiaque et cardioprotection
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 consantly 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 pronostic factor of morbidity and mortality. Our research team focuses on the cellular mechanisms underlying the genesis and control of cardiac automaticity and to elucidation of 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 to protects 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 L-type Cav1.3 and T-type Cav3.1 calcium channels in cardiac automaticity and coduction in mice and humans (see Mangoni and Nargeot Physiol Rev 2008 : 88, 919-982 for review). 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 pronostic factor of mortality and constitutes, together with stroke, the principal cause of cardiovascular mortality. The infarct size is an important prognostic factor of mortality. By associating protocols inducing cradioprotection on animal models and in clinical trials, we aim to identify new candidate genes and pharmacological tools for fighting against ischemi-reperfusion injury, so to reduce infarct size. In paricular, we target mechanisms undelying lésion induced apoptosis.