Acquired CCN2 deficiency alters aortic structure and increases susceptibility to Ang II-induced aneurysm formation
The impact of CCN2 deficiency on aortic remodeling and the time-course of aneurysm formation in response to Ang II were evaluated by in vivo magnetic resonance imaging (MRI) in a 1 cm section from the superior mesenteric artery. Angiography analysis confirmed the generation of dissecting aneurysms in CCN2-KO mice in response to Ang II administration, which occurred in some mice as early as at 48 hours (Figure 2A and Suppl Figure 3). These aneurysm-related structural changes include patchy reductions of the aortic lumen associated with increased total aortic area (Figure 2B ), which could result from medial dissection. Maximum total aortic area and minimum aortic lumen were significantly modified in Ang II-infused CCN2-KO mice after 24 and 72 hours of treatment, respectively (Figure 2C and D). In another set of mice experiments, aneurysm formation was followed until 15 days by ultrasound imaging. The echography measurements confirmed that Ang II infusion significantly increased the thoracic ascending aorta (TAsA) and abdominal aorta (AbA) diameters, showing the presence of TAAAs (Figure 3A and B ).
Importantly, the evaluation of CCN2 deletion effect in the aorta in physiological conditions (in the absence of the pathological stimuli Ang II) by both MRI and ultrasound imaging revealed a key role of CCN2 in aortic homeostasis. MRI evaluations in CCN2-KO mice showed a significant but slight increase in the maximal total area and in the minimum aortic lumen compared to WT mice (Figure 2C and 2D) , indicating aortic dilatation in absence of CCN2. Additionally, ultrasound imaging measurements confirmed this increment in the AbA diameter in CCN2-KO mice compared to WT (Figure 3A and B ).