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Dr. Jean-Sebastien Hulot
View the Slides from this session in ESC Congress 365
The session has focused on new mechanisms supporting myocardial responses to adrenergic stimulation. Beta-receptors blockers or agonists are essential medications in the management of diverse cardiovascular conditions. New data on receptors coupling, differences associated with beta-receptors subtypes and downstream effectors can help us refine the use of these medications.
Prof. M Zaccolo (Oxford, GB) explained how the production of the second messenger cyclic AMP in response to an adrenergic stimulation is compartmentalized into different subcellular microdomains. Importantly, the localization in some specific pool leads the same second messenger to control different cellular functions. Different phosphodiesterases isoforms contribute to maintaining these pools in some specific compartments and their targeting could lead to new therapeutic options for myocardial disorders.
Dr. G. Corbi (Campobasso, IT) showed the role of GRK2 to control the activity and the kinetics of beta-adrenereceptors. Manipulating GRK2 appears to be a new strategy in strengthening the response to beta-adrenergic drugs.
Dr. A. Ghigo (Turin, IT) similarly discussed the role of PI3Kgamma as a kinase-anchoring protein that will further regulate the beta2-dependent cyclic AMP production. In a murine model, PI3Kgamma appears as critical to limit the arrhythmogenic events induced by beta-adrenoreceptors stimulation. The scaffolding activity of PI3Kgamma has been particularly highlighted.
Prof. Sian Harding (London, GB) reported on Tako-Tsubo, a cardiomyopathy induced by a very high surge in plasma catecholamine levels in response to stress. The clinical presentation is similar to an acute coronary syndrome (without coronary artery stenosis) associated with systolic dysfunction specifically affecting the apical and mid-left ventricular walls. Prof. Harding has shown how the disease might be explained by beta2-adrenoreceptor switching from Gs to Gi coupling, thus activating cardioprotective but cardiodepressant pathways.
In summary, the understanding of beta-receptor signalling is an evolving area that can help in tailoring the use of drugs targeting beta-receptors. Targeting new downstream effectors will be a complementary approach.
Novel insights into myocardial responses to adrenergic stress, Science in Practice on autonomous control and the heart
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