Does YAP/TAZ signalling play a role in right-left ventricular interactions?

• Applicant: Dr. Sonja Raschzok
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2019 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 436830268

Heart failure is the fastest rising cardiovascular disease, with a projected 25% increase over the next decade and a 25-50% one-year mortality. Treating left ventricular (LV), right ventricular (RV) and pulmonary vascular (PV) function separately has not improved outcomes. Friedberg et al. have shown in rodent models that constricting the pulmonary artery to cause RV failure leads to LV fibrosis and dysfunction. Aortic constriction causes LV failure and leads to RV fibrosis and dysfunction. Consequently, LV and RV function and failure cannot be regarded as separate entities. As the pulmonary bed lies between the left and right circulations, the lungs are an important component of RV-LV interaction. However, the molecular signalling that transmits mechanical stress of RV or LV failure into contralateral ventricle is not completely understood. The proposed project is to define the role of YAP/TAZ signalling, a powerful mechanotransducer known from pulmonary hypertension, in development of fibrosis and remodelling in RV-LV interactions. As YAP/TAZ signalling can be pharmacologically modulated, this novel and exciting approach has high potential for rapid clinical translation. A rodent animal model of RV-LV interactions as well as primary cell culture models, which mimic mechanical stress, are established in the Friedberg laboratory and will be harnessed for the aims of this proposal.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Professor Dr. Mark Friedberg