Impact of platelet-derived exosomes in atherosclerosis-related diseases with emphasis on aortic aneurysm

• Applicant: Dr. Agnesa Mazrekaj
• Subject Area: Cardiac and Vascular Surgery
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 563407405

An aortic aneurysm describes a pathological dilation of the aorta which, if left untreated, can lead to progression with a consecutive risk of rupture, which is associated with a high mortality rate. The complex interactions that lead to the development and progression of an aortic aneurysm continue to be the subject of intensive basic scientific and clinical research. The weakening of the three-layered aortic wall is promoted by a destruction of elastic fibers and the breakdown of smooth muscle cells due to inflammatory processes. Extracellular vesicles, which can be released by various cells and act as mediators, are of special interest. They are divided into subgroups according to their size. Among the extracellular vesicles, exosomes are the smallest in size but have the greatest potential for intercellular communication. In particular, exosomes, which are secreted by platelets, are the focus of research in the development and progression of aortic aneurysms. Previous sequencing experiments have shown that platelet-derived exosomes, that are isolated from the blood of patients suffering from an aortic aneurysm or carotid artery stenosis influence a potential change in the transcription process. To continue these in vitro studies and confirm them in an in vivo model, a murine model will be used. After isolation of platelet-derived exosomes from the blood of the mice, there will be an infusion of the infrarenal aorta with these exosomes to induce an aneurysm. This model will be compared in parallel with the already established model for induction of an infrarenal aortic aneurysm using pancreatic elastase. Subsequently, a histological and immunohistochemical examination of the tissue will be performed. An analysis at RNA and protein level is also planned. If the results are insufficient, there will be further experiments using a known exosome inhibitor in order to disable exosome secretion. This will be followed by the aforementioned tissue, RNA and protein analyses. Based on the project described above, new findings on the development and progression of the aortic aneurysm are to be determined.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Philip Tsao, Ph.D.