Evaluation of gene specific proteins found in thoracic aortic aneurysm and thoracic aortic dissection patients by immuno-histological staining

Background: Despite state-of-the-art medical care, acute aortic dissections are among the most dangerous diseases of the cardiovascular system. Due to rapidly occurring complications such as pericardial tamponade, rupture or ischaemic organ damage aortic dissections are associated with a very high mortality rate. While risk factors that lead to aortic dissections are well known, the underlaying pathomechanical influences that lead to destabilisation of the aortic wall remain unclear in key aspects. Nowadays it is assumed that immunological influences play an important key role in destabilisation of the aortic wall. In a previous study by Doppler et al., 37 genes were identified that were dysregulated in at least three previous studies. In gene expression analysis five of the genes were upregulated in TAD compared to the control group, but only CXCL8, and IL6R were significantly upregulated. When TAD was compared with TAA, all genes showed increased expression on TAD, but only IL6R was significantly upregulated. Therefore, the current thesis focuses on identifying the proteins for these 4 genes found to be significantly affected by immune response and especially the three (CXCL8, IL6R and CCL2) which were found in both TAA and TAD. TAA patients, TAD patients, and control patient samples, which were also used in the above-mentioned study, will be analysed by immuno-histological staining to prove the distribution and quantity of proteins specific for the above-mentioned genes. Methods: Paraffin embedded patient tissue of TAV-TAD and TAA-TAD, TAA from thoracic patients compared to control patient were subjected to antibody-ligated fluorescence targeted protein identification followed by fluorescence-microscopy and data evaluation. Therefore, the patient tissue was sliced with the usage of a microtome. Followed by fluorescence staining, microscopy and evaluation to which extent the above-mentioned markers (proteins) were present in the different manifestation of coronary artery diseases. Results: A DAPI normalised fluorescence analysis for the target proteins revealed significant upregulation of FABP4, IL6R, IL8 and MCP1 in thoracic aortic dissection compared to control, whereas TIM-3 only showed minor changes. These findings highlight the potential as markers for thoracic aortic diseases and provide a foundation for future studies on early detection and risk stratification.