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AG Hirt
Name: Prof. Dr. Dr. Marc Hirt
Institute/Center: Institute of Experimental Pharmacology and Toxicology, University Center of Cardiovascular Science (UCCS)
Email:
m.hirt@uke.de
Research Focus and Main research questions
Cardiac hypertrophy is the most important risk factor for the development of heart failure which is the leading cause of death in industrialized nations. We aim to decipher some of the molecular mechanisms of cardiac hypertrophy by a model of cardiac hypertrophy which we have developed over the past couple of years. It is based on engineered heart tissue (EHT), a 3-dimensional cell culture format for heart cells, which we subject to enhanced workload thus inducing phenotypical characteristics of cardiac disease.
The idea behind our cardiac hypertrophy model is the enhancement of afterload/workload (AE = afterload enhancement) of these small tissue strips by a simple mechanical metal brace. Most fascinating is that engineered heart tissues (EHTs) beat spontaneously. In contrast to simple cell cultures of cardiomyocytes EHTs provide therefore the optimal assay to assess the essential cardiac properties frequency and force, which can be analyzed automatically with technologies developed in our institute. “And it works!” The model of cardiac hypertrophy displays in vitro many aspects of cardiac hypertrophy/heart failure: Cardiomyocyte hypertrophy, fibrosis, metabolic changes towards glycolysis, characteristical changes in coding and noncoding RNAs and many more. Future directions: The next step we are working towards is the transition of this model of cardiac hypertrophy from rat heart cells to human heart cells. For this endeavor, we take advantage of the latest advances in stem cell technology.
The discovery of human induced pluripotent stem cells made it – in principal - possible to create all cell types in the human body including all types of human heart cells without ethical concerns or animal experiments. We have been able to create fluorescently labeled human multi-cell-type EHTs containing blue cardiomyocytes, green endothelial cells, orange smooth muscle cells and red fibroblasts. Lately, macrophages differentiated from pluripotent stem cells have been added to our portfolio of cells. EHTs in combination with a magnetics-based device that enables us to modulate stepwise increases in workload enable us to analyze the impact of timing and magnitude of afterload on human heart tissue to deeply investigate pathological cardiac hypertrophy (like in heart failure) and potentially even physiological cardiac hypertrophy (like in an athlete’s heart).