Abstract MP18: Mitochondrial Inducing Factor 1 Affects Stabilization Of Advanced Atherosclerotic Lesions In Carotid Artery Disease

Whereas cerebrovascular diseases, most and foremost ischemic events, being the second most deadliest disease as of today in the western world the process behind carotid artery plaque (CAP) vulnerability remains understood insufficiently. Through proteomic analysis of blood serum from patients treated for atherosclerotic lesions in carotid arteries we were able to determine proteins of potential relevance to CAP stability. One of the identified targets is mitochondrial apoptosis inducing factor 1 (AIFM1), which we found upregulated in serum profiles from patients with vulnerable atherosclerotic lesions. The study were conducted with human vascular tissue and blood samples from the 'Munich Vascular Biobank'. Proteomic profiling of serum was performed using the platform OLink (Uppsala, Sweden) taken from patients with either stable (n=53) or unstable (n=53) CAPs. Furthermore, gene expression of AIFM1 in stable (n=5) and unstable (n=3) CAPs was assessed via RT-qPCR .Via Immunostaining the regions showing higher expression of AIFM1 within the plaques (n=10) were determined and put in perspective with markers of cell types predominantly accumulated in those regions. In addition, blood monocyte-derived macrophages were stimulated with different factors and changes in expression of AIFM1 was assessed. With the proteomic sequencing of blood sera, higher levels of AIFM1 in patients with unstable versus stable CAP were determined. This trend was also seen assessing the gene expression of AIFM1 in the human vascular tissue. A significant enrichment of staining of AIFM1 positivity was observed in regions where apoptosis occured, such as the necrotic core and the shoulder regions of the advanced CAP. Furhtermore, AIFM1 enriched regions were identified as areas infiltrated by immune cells, especially macrophages. Monocytes of healthy donours showed an increased expression of AIFM1 when developed into macrophages. In conclusion AIFM1 was identified as a potential novel marker for advanced, unstable lesions in CAPs. Future studies (in vitro and in vivo) will reveal which role AIFM1 might play during processes that trigger CAP destabilization. Of further importance will be cell type expression patterns that we are also assessing in currently ongoing studies.