Project Details
Projekt
CTRP9 from the heart: Impact on cellular signal transduction, myocardial remodeling, systemic insulin resistance and prospects for gene-therapy approaches.
Subject Area
Cardiology, Angiology
Term
from 2013 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 234125093
Chronic heart failure is a common and deadly disease. Epidemiologic data reveal an increasing prevalence of diabetes among heart failure patients. On the one hand diabetes with insulin resistance can lead to heart failure, but on the other hand heart failure itself predisposes to the development of insulin resistance and diabetes. It has been proposed in this regard that endocrine factors released from the heart influence systemic metabolism (e.g. in skeletal muscle) and insulin resistance. During screening for cardiac secreted factors we identified the glycoprotein CTRP9, which exerts homology to adiponectin, and which is preferentially expressed in the heart and released into the circulation. Interestingly, systemic overexpression of CTRP9 was shown to reduce serum glucose levels. We found cardiac CTPR9 to be specifically upregulated during compensated cardiac hypertrophy, but not heart failure. Our preliminary data show a prominent anti-hypertrophic role of CTRP9 in cardiomyocytes. Cardiac hypertrophy emerges during diabetes and also arterial hypertension and predisposes to the development of heart failure. We propose that CTRP9 from the heart improves systemic insulin resistance and prevents the development of cardiac dysfunction locally in the myocardium. Here, we aim to identify receptors, intracellular signalling, transcription factors and target genes activated by CTRP9 in cardiomyocytes, skeletal muscle, liver and fat cells. Furthermore, we will use CTRP9 knock-out mice and gene-therapy driven myocardial CTRP9 overexpression to investigate its impact on systemic metabolism and insulin resistance as well as myocardial remodelling during the development of heart failure due to cardiac pressure overload or metabolic stimulation.
DFG Programme
Research Grants
