Zu den Inhalten springen
Universitäts-Herzzentrum Freiburg - Bad KrozingenUniversitäts-Herzzentrum Freiburg - Bad Krozingen

In the past decade, a new class of gene expression regulators has emerged: microRNAs. These small non-coding RNAS regulate gene expression on a post-transcriptional level and one microRNA is able to regulate several independent or functionally related mRNA target genes, thereby modulating broad range of biological processes and pathological disorders. Our focus in this research area lies on microRNA function in cardiovascular occlusive diseases and we develop new therapeutic strategies for cardial protection and healing based on either microRNA substitution or inhibition.

MicroRNAs in chronic vascular inflammation

Vascular inflammation is not only a critical component of the host –defense reaction against external pathogens and injury, but also an important modulator of pathological conditions such as atherosclerotic lesion formation. We are interested in the function of microRNAs in processes relevant for chronic vascular inflammation such as endothelial-leukocyte interaction, homing and migration of immune cells and their modulation of pro- as well as anti-inflammatory signaling cascades. We also investigate the impact of either microRNA inhibition or overexpression on atherosclerotic lesion formation and the plaque phenotype.

MicroRNAs in ischemia-reperfusion injury

Ischemia-reperfusion injury is the term for a harmful inflammatory process occurring during restoration of blood flow following a critical time of ischemia. I/R-injury plays an important role in different clinical setting such as myocardial infarction, stroke as well as transplant surgery. Ischemia-reperfusion is determined by different components such as the infiltration of circulating cells in the injured tissue and the local generation of reactive oxygen species. We investigate the role of microRNAs in ischemia-reperfusion injury using two different in vivo models: temporary occlusion of the left anterior descending artery for induction of myocardial infarction in the mouse heart and the preparation of the cremaster muscle to allow the in vivo imaging of endothelial-leukocyte interaction. Both models combined with histological and gene expression analysis are used for the characterization of microRNAs in the process of harmful and protective mechanisms during ischemia and reperfusion.

MicroRNAs in in stent-restenosis and arterial remodelling

Restenosis describes the narrowing or occlusion of a blood vessel for example following coronary stent implantation and it is caused by a proliferation of vascular smooth muscle cells (VSMC) into the lumen. VSMCs control the organisms` circulatory homeostasis by regulating the tone of arteries and arterioles and can switch between two phenotypes: contractile and synthetic. The latter is a critical part of embryonic and fetal development as well as physiological adaption to pregnancy and exercise, but can also be a harmful response to vascular injury due to atherosclerosis, hypertension or percutaneous coronary interventions. We investigate the impact of microRNAs on the phenotype switch of VSMCs in vitro as well as on neointima formation in vivo.

MicroRNAs in energy metabolism

In industrial countries, the number of people developing a metabolic syndrome is rapidly increasing and is mainly caused by an unfavorable lifestyle in combination with genetic predispositions. In the last years, microRNAs came into the focus in this area of research and so far several microRNAs have been reported to be involved in the regulation of metabolic processes. Our group focuses on the investigation of microRNAs in the regulation of key metabolic mRNAs and their proteins and our goal is to define their function in the development of age related diseases like diabetes and obesity.

MicroRNAs and adaptive neovascularization

The adaptive growth of arteries is an important protective mechanism in patients with vascular occlusive disease. We investigate the molecular mechanisms regulating this process and attempt to stimulate the growth of capillaries and collateral arteries as a possible future therapeutic approach. Angiogenesis (the growth of capillaries) and arteriogenesis (the growth of arteries) involves the complex interactions of different cell types, including endothelial cells, smooth muscle cells and circulating cells, especially infiltrating monocytes and macrophages. We are especially interested in the use of microRNA therapeutic to stimulate pro-arteriogenic processed without unwanted side effects on angiogenic tumor growth.

Labor

Prof. Dr. Grundmann

Telefon: +49 761 270-70460
Telefax: +49 761 270-70450