Identification and Validation of Novel Inotropy-Enhancing Molecular Targets


Funding ID

81Z2500205

Project number

468

Institution
Ruprecht-Karls-Universität Heidelberg
Project leader
Thomas Wieland
Site
Heidelberg/Mannheim
Short description

In this project molecular targets in a novel positive inotropic pathway coupling M2 muscarinic receptors to RhoA/Rho-kinase in heart failure are characterized and validated. The so far … 

In this project molecular targets in a novel positive inotropic pathway coupling M2 muscarinic receptors to RhoA/Rho-kinase in heart failure are characterized and validated. The so far identified targets are the Regulator of G-protein signaling RGS3, the RhoGTPase-actvating protein p190RhoGAP and the guanine nucleotide exchange factor Tiam1. Depending on the expression level of RGS3 this proteins allow for a switch of the coupling of M2 muscarinic receptors to a Rho-kinase dependent positive inotropic response in cardiac myocytes. Therefore, all three proteins are putative molecular targets for novel therapies in heart failure.

Project type
Partner Site Projects
Keywords
cardiac contractiliy,muscarinic receptors, RhoGTPases, RhoGTPase-activating proteins, RhoGTPase guanine nucleotide exchange factors,
Topic
cardiomyocyte function
Funding
€ 611.112,45
Begin
01.01.2015
End
31.12.2018