Diagnostic and Prognostic Blood Test for Ascending Thoracic Aortic Aneurysms.
I ntroduction-Purpose: Thoracic aortic aneurysms are the second most common kind of aneurysm. In most cases aneurysms are growing without symptoms and the diagnosis happens incidentally with the help of imaging exams, while searching for other issues. The natural evolution of the disease is followed by high percentage of mortality (rupture or aortic seperation). All these facts dictate the need for the development of a simple, reliable, safe and non invasive diagnostic test.
M aterials-Methods: Histology samples coming from aneurysms that don't relate to genetic syndroms (e.g. Marfan, Loeys-Dietz, etc) as well as samples from peripheral venous blood were collected from 42 patients who have undergone surgery of replacement of aneurysms of ascending thoracic aorta. Moreover, blood samples were collected from 13 patients without aneurysmatic disease, something that was proved with the help of imaging exams. Patients were categorized into 3 groups depending on the diameter of aneurysm: diameter 5-6cm (n=21), diameter 6-7cm (n=13) and diameter > 7cm (n=8). The quantitative expression of the mRNA levels of the 15 genes analyzed, that are involved in the remodeling of the extracellular matrix of aortic wall were measured through real-time qRT-PCR.
R esults: The 15 genes that were analyzed relate to genes that codes for specific chains of collagen (COL11A1, COL5A2, COL5A1, COL3A1, COL1A1, COL1A2), integrin receptors (ITGA3, ITGA4, ITGA6, ITGB1), metalloproteinases (MMP2, MMP9, TIMP1) and control genes (BMP1, TGFB1). From the total of 15 genes a subgroup of 8 genes (COL11A1, COL5A2, ITGA4, ITGAB1, MMP2, MMP9, BMP1 and TGFB1), had the most dramatic changes. By measuring the levels of these 8 genes in the peripheral blood, the distinction of patients with ascending thoracic aortic aneurysm in comparison to the control group (normal diameter of ascending aorta), was achieved with a sensitivity of 95% (95% C.I. 0.89-1.00, P<0.001) and a specificity of 92% (95% C.I. 0.78-1.00, P<0.001). Additionally, it was possible to distinguish between patients with aneurysms of large diameter and patients with aneurysms of smaller diameter with a sensitivity of 95% (95% C.I. 0.86-1.00, P<0.001) and a specificity of 86% (95% C.I. 0.71-1.00, P<0.001), a fact that dictate the prognostic value of the blood test.
C onclusions: The prognostic and diagnostic blood test, that our team developed, is at the stage of patent granting, so that the next steps can begin in order to achieve immediate clinical application.
Early detection saves lives as aneurysms most often times can be treated
Our blood test can be used repeatedly used, without negative consequences for the patient, monitoring the disease and providing clear results about it's progress.
A silent killer
The aneurysm can suddenly break and most of the time the patient dies due to massive internal bleeding.
It is calculated that around 1% – 2% of the population has aortic aneurysm most of them are being undiagnosed.
The disease does not have any early symptoms.