Smooth muscle specific role of SDF-1 in cell recruitment and cardiac repair after MI

Heart Diseases are the main reason for mortality in the Western world. Heart failure following myocardial infarction is the most prevalent. Although new medical therapies can reduce the progression of diseased hearts to chronic heart failure, once lost, replacement of functional myocardium is very limited. Therefore, therapies to augment and preserve myocardial tissue are warranted. Ongoing research suggests a fundamental role of the cell recruitment factor SDF-1 and its receptor CXCR4 in cardiac repair after myocardial infarction. Recently, we could demonstrate that inhibition of stromal derived factor-1 (SDF-1) degradation after myocardial infarction (MI) improves myocardial function and may even enhance cardiac regeneration. Nevertheless, the precise cellular mechanisms how SDF-1 dependent cell migration is orchestrated remains barely understood. Since our preliminary data reveal severely increased hearts when the important cell recruiting factor SDF-1 is knocked out in vessels, we aim to investigate the impact of this knock-out on heart function and cell recruitment after myocardial infarction. The knock-out will be induced during embryonic development but also in the adult heart. In a 2nd aim we are investigating the impact of SDF- 1 overexpression in vessels on heart function. In the 3rd aim we created a novel mouse model to visualize CXCR4+ cells in the heart at any particular time point to monitor their cell fate. In this model we aim to test a new drug for the prevention of heart failure. Cell recruitment will be analyzed utilizing flow cytometry, myocardial remodeling will be determined by immunohistology and measurement of heart function by millar-tip microcatheters. Differentially expression of genes will be determined by Deep Sequencing technology. Ultimately, these new approaches might lead to the development of novel therapies for heart failure.