Baldus, Stephan - assoc. RG 01

Heart failure (HF) is one of the most important drivers of cardiovascular mortality. Ischemia- (IHF) and chemotherapy-induced heart failure (CIHF) share similar routes of maladaptive cardiac remodeling, accompanied by 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, specific anti-inflammatory therapies in cardiovascular disease could not be established so far, probably due to an incomplete understanding of the mechanistic link between inflammation and cardiomyocyte function. We identified the leukocyte-derived heme enzyme myeloperoxidase (MPO) as a biomarker for the outcome of patients suffering from ischemic and cardiotoxic injury and as a potent propagator of fibrotic myocardial remodeling (Fig.1A, B).

Of note, we could elucidate that MPO is an integral constituent of extracellular vesicles (EV), a recently identified type of circulating signalling mediator, which regulate the innate immune response after cardiac injury.

Herein, we not only aim to characterize the function of MPO in modulating the innate immune response, but also to dissect the role of MPO-competent EV as novel signalling mechanisms in IHF and CIHF. Given current preclinical efforts in the development of specific MPO-inhibitors, this project will help to elucidate the role of MPO in adverse ventricular remodeling in HF and for the first time characterize the role of EV as vectors for myocardial MPO delivery in cardiac disease.

As therapy for acute myocardial infarction and chemotherapeutic strategies for cancer improve, the incidence and mortality of IHF and CIHF has increased. Given that MPO emerged as a crucial pro-inflammatory player in cardiovascular diseases, we will investigate its significance in leukocyte activation and extracellular vesicle-signalling in HF, which might become therapeutically relevant in the prospect of applying pharmacologic MPO-inhibitors.

As therapy for acute myocardial infarction and chemotherapeutic strategies for cancer improve, the incidence and mortality of IHF and CIHF has increased. Given that MPO emerged as a crucial pro-inflammatory player in cardiovascular diseases, we will investigate its significance in leukocyte activation and extracellular vesicle-signalling in HF, which might become therapeutically relevant in the prospect of applying pharmacologic MPO-inhibitors.

For more information about Prof. Baldus´ work, please check this research site.