Modulation of cAMP microdomains to treat heart failure
- Universitätsklinikum Hamburg-Eppendorf
- Viacheslav Nicolaev
The ubiquitous second messenger cAMP plays central roles in the regulation of cardiac function and diseases such as hypertrophy and heart failure. Especially the stimulation of cardiomyocyte ?-adrenoceptors leads to strong contractile response and disease progression, while other membrane receptors coupled to the stimulatory G-protein (Gs) play less prominent role. Beta-blockers are therefore central to the therapy but lead to non-cardiac side-effects which limit patient compliance. This project will test the hypothesis that cardiomyocyte-specific delivery of a dominant negative Gs mutant should provide beneficial antihypertrophic effect without systemic side-effects. This mutant will be studied in mouse diseased models and introduced into AAV for gene therapy studies.
- cAMP, microdomains, hypertrophy, beta-blocker, AAV, genetherapy
- cardiac hypertrophy/remodeling
- € 491.801,84