Transcriptional control of cardiac function and bioenergetics regulatory circuits by type I interferon signaling

• Applicants: Dr. Manju Kumari; Privatdozent Dr. Ashraf Rangrez, Ph.D.
• Subject Area: Cardiology, Angiology ; Biochemistry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 517822362

Activation of pro-inflammatory pathways and mitochondrial dysfunction has been implicated in the pathophysiology of heart failure (HF). Recently, interferon (IFN) stimulated genes have been identified as novel biomarkers of ischemic cardiomyopathy in humans. However, the role of interferon signaling in regulating cardiomyopathy is not well understood. Importantly, we found activation of transcription factor IRF3, a key transcriptional activator of type I IFN-signaling, in the heart of patients with ischemic cardiomyopathy. Despite a well-known role of IRF3 regulating glucose and energy homeostasis in fat and liver tissues, little is known about whether and how IRF3 driven type I IFN signaling alters cardiac immunometabolism. Based on very interesting preliminary results, we here hypothesize that IRF3 controls transcriptional network in the heart regulating mitochondrial function and cardiocrine signalling in myocardial infarction via yet unknown mechanisms. Thus, using cell-type specific approach, we here aim to gain thorough understanding of the type I IFN-signaling activation dependent intracellular consequences on mitochondrial bioenergetics in cardiomyocytes and identify potential cardiokines reshaping cardiomyocytes microenvironment in the heart.

• DFG Programme: Research Grants