The role of myeloperoxidase in inflammatory processes and macrophage activation in heart failure

• Applicant: Martin Mollenhauer, Ph.D.
• Subject Area: Cardiology, Angiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437042528

Heart failure (HF) is the most important factor of cardiovascular mortality in Western industrialized countries. Ischemia- (IHF) and chemotherapy-induced heart failure (CIHF) share similar routes of maladaptive cardiac remodeling upon deterioration of cardiomyocyte function. Although leukocytes in general and polymorphonuclear neutrophils (PMN) in particular are abundantly located to the myocardium after ischemic- and cardiotoxic injury, a mechanistic link between the innate immune response and left ventricular function remains unclear and anti-inflammatory therapies still have to be established. Leukocyte activation, especially of PMN, leads to the release of the pro-inflammatory enzyme myeloperoxidase (MPO), with a subsequent angiotensin II (AngII) -depended recruitment of monocytes into the damaged myocardium. MPO has been identified as a biomarker for the outcome of ischemic- and cardiotoxic injury patients and as a potent propagator of maladaptive myocardial remodeling and is furthermore an integral component of extracellular vesicles (EV), a recently identified type of signalling mediators, regulating the innate immune response after cardiac injury.Herein, we aim to characterize the function of MPO in modulating the innate immune response and AngII-dependent leukocyte recruitment. We will furthermore dissect out the role of EV and MPO-competent EV as novel signalling mechanisms in IHF and CIHF. Given the recent preclinical efforts in the development of specific MPO-inhibitors, this project will help to elucidate the role of MPO in modulating the innate immune response in IHF and CIHF and will characterize the role of EV as vectors for myocardial MPO delivery.

• DFG Programme: Research Grants
• International Connection: Czech Republic
• Cooperation Partner: Dr. Lukas Kubala