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Exploration of a novel biomarker for thoracic aortic aneurysm and dissection.

A progressive widening of the aorta (called aortic aneurysm) affecting our body's main blood vessel in the chest (thorax) can lead to a catastrophic event with a tear or rupture of the aortic wall (dissection or rupture). Unfortunately, a thoracic aortic aneurysm most often remains asymptomatic until catastrophic dissections or ruptures happen. These latter complications are a major cause of sudden cardiac death in the western world. Currently, aortic aneurysms are mostly detected incidentally upon imaging studies for other medical indications. Although not perfect, follow-up of the diameter of the aorta by imaging studies is considered the best predictor of the aortic dissection risk. At present, there are no markers in the blood (called biomarkers) that can predict the presence of a thoracic aortic aneurysm or the occurrence of a thoracic aortic dissection. Identification of such a biomarker would be of great help in the faster and easier diagnosis and follow-up of thoracic aortic aneurysm and dissection. Upon investigation of aneurysmal aortic gene expression profiles of three different symptomatic mouse models of Marfan and Loeys-Dietz syndrome, we observed high expression of a novel gene in all three models. This gene encodes for a growth factor that has not previously been associated with the pathogenesis of thoracic aortic aneurysm. Although the molecule has been linked to metabolism and cancer, its highest expression is in the aortic wall. In this study we would like to investigate if serum levels of this growth factor in Marfan and Loeys-Dietz syndrome mice correspond to their thoracic aortic aneurysm severity and progression. We will validate the findings in serum samples of patients with thoracic aortic aneurysm and dissection. If successful, the latter model can be used in future projects to test therapeutic compounds with the "simple" measurement of the levels of this growth factor as the outcome parameter. In summary, if successful our project will provide the strong foundations of future research that will further explore whether serum levels of this growth factor can detect asymptomatic thoracic aortic aneurysm, monitor disease progression and predict aortic dissection.
Date:1 Sep 2022 →  Today
Disciplines:Biomarker evaluation