Thoracic aortic disease: Identification of diagnostic circulating biomarkers using proteomics

• Applicant: Dr. Till Joscha Demal
• Subject Area: Cardiac and Vascular Surgery
• Term: from 2022 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 499174645

Thoracic aortic aneurysms (TAA) are associated with life-threatening complications such as dissections and ruptures and lead to 10,000 to 20,000 deaths per year in Germany alone. Aneurysms are asymptomatic in 95% of the cases before serious complications occur.Although several biomarker candidates have been evaluated for the early detection of aneurysms in the past, none of these candidates could be transferred to clinical application due to a lack of validating data. Since thoracic aortic diseases are pathologies of the extracellular matrix (ECM), we propose to specifically analyze proteins expressed in the aortic ECM to identify new potential biomarkers.The analysis is carried out in the whole blood of 40 patients with TAA and 40 healthy controls. As part of a targeted proteome analysis, 103 known ECM proteins are tested on differential concentrations between diseased and healthy probands. In addition, exosomes are evaluated as potential biomarkers. Furthermore, 27 previously described biomarker candidates are validated. Finally, a possible correlation of the biomarker concentrations with the aneurysm diameter, the patient's age and the histological severity of the disease will be analyzed.Identifying and validating a biomarker for TAA would enable the screening for thoracic aortic disease in high-risk patients in the future. Here, biomarker concentrations could reflect the degree of aortic dilatation. The timely diagnosis of TAA could subsequently enable an individual drug or surgical therapy to prevent life-threatening complications.

• DFG Programme: Research Grants