Principal Investigator
Director of Department III of Internal Medicine
Immune cells and their enzymatic armamentarium not only have the capability of irreversibly degrading tissue, they also interfere with signaling pathways in the cardiovascular system, thus evolving as a potential pharmacological targets
Atherosclerosis, aortic aneurysm formation, heart failure, arrhythmias such as atrial fibrillation and ventricular tachycardia all have been linked to activation of the innate and acquired immune system. We aim at in depth characterizing the role of immune cells to decipher their impact on signaling in conductance and resistance vessels, on myocardial fibrosis and the cardiomyocytes electrical homogeneity. The goal is to identify pharmacologically addressable targets to prevent atherosclerotic lesion development, cardiomyocyte dysfunction and electrical instability of the atria and ventricles and remodeling of large conductance vessel such as the aorta.
Our group aims at increasing the understanding of the role of immune cells in atherosclerotic disease, myocardial failure and arrythmias with the ultimate goal to identify specific pharmacological targets
Our group aims at characterizing the role leukocytes for vascular dysfunction, cardiomyocyte failure and arrhythmogenicity of the heart.
We are following the idea, that leukocytes, e.g. neutrophils and their respective enzymes, contribute to cardiovascular disease e.g. by interfering with signaling pathways within the endothelium and within cardiomyocytes. Increased vascular tone provoked by leukocyte activation and vascular sequestration of enzymes might be lifesaving during acutes states of sepsis, but detrimental in the context of chronic leukocyte activation such as in coronary disease or in the context of heart failure.
In this regard we have made observations that myeloperoxidase (MPO), an enzyme abundantly expressed by and released from neutrophils, indeed modulates vascular tone by oxidation of nitric oxide, accelerates ventricular and atrial remodeling by promoting fibrosis and affects homogeneity of the aortic wall propagating aneurysm formation. We teamed up with pharmaceutical companies to inhibit the enzymatic activity of MPO rodent models of disease. Finally, to translate these findings into a treatment strategy in humans, we are currently conducting a phase 2 randomized placebo controlled double blind multi-center trial to test the role of MPO inhibition in patients with advanced symptomatic systolic heart failure.
Eiserich*, Baldus* et al. Science 2002 *equal contribution
Rudolph, ..., Baldus et al. Nature Med 2010
Klinke, ..., Baldus JCI insight 2018
Nettersheim, ..., Baldus et al. Cardiovasc Res 2022
Nettersheim, ..., Baldus, et al. Bas Res Cardiol 2023
Principal Investigator
Director of Department III of Internal Medicine