Ascending thoracic aortic aneurysm (ATAA) is a life-threatening cardiovascular disease, leading to weakening of the aortic wall and permanent dilation. ATAA affects approximately 10 out of 100,000 persons per year in the general population, and this disease is associated to high risk of mortality and morbidity. The degeneration of the arterial wall at the basis of ATAA is a complex multifactorial process. Individual genetic, biological or hemodynamic factors are inadequate to explain the heterogeneity of ATAA development/progression mechanisms, thus stimulating the analysis of their complex interplay. We established a methodology to quantify non-invasively local stiffness properties of ATAAs using electrocardiographic-gated computed tomography (ECG-gated CT) scans. We showed strong relationship between the extensional stiffness and the rupture stretch of the aortic tissue, supported by biomechanical explanations. Then we discovered the interrelationship between the obtained local stiffness with other established markers of aortic function such as intravascular flow structures. The observed interrelationship corroborate computational predictions of ATAA progression coupling hemodynamics with mechanobiology after hemodynamic insult. Recently, we eventually related these results to the existence of a specific smooth muscle cell phenotype found in ATAA, exhibiting stronger traction forces and thicker morphologies.