Pulse Wave Imaging for Assessing Arterial Stiffness Change in A Mouse Model of Thoracic Aortic Dissection in Marfan Syndrome

Marfan syndrome (MS) is a hereditary connective tissue disease characterized by the defection of collagen complex and decrease of the connection between collagen and elastic fibers. Thoracic aortic dissection (TAD) is a common cause of death for patients with MS. In this study, we performed pulse wave imaging (PWI) in a beta-aminopropionitrile (BAPN) induced, MS-relevant mouse model of TAD and measured the pulse wave velocities (PWVs) to assess the aortic stiffness related to the occurrence of TAD in MS. Three-week-old male mice were fed with regular diet (control group, n = 6) and diet with BAPN (BAPN group, n = 10) for 20 days, respectively. BAPN inhibits the cross-linking of collagen and elastin in systemic arteries, similar to TAD in MS patients, and could induce the occurrence of TAD in mice. PWI of the proximal abdominal aorta was performed every two days with a SonixMDP system and an L40-8 probe. Focused wave imaging with a reduced beam density was used to obtain a high frame rate of 980 Hz. The distension velocities of the aortic wall were estimated using speckle tracking and PWVs at the systolic foot (PWV_sf) and dicrotic notch (PWV_dn) were measured in vivo. Histologic examinations were performed on the thoracic aorta to confirm the presence of TAD. Statistical significance was assessed using two-tailed t tests. After 20 days of feeding, 8 mice from the BAPN group were found to have TAD in the histologic examinations. No significant differences in PWV_sf and PWV_dn were found between the control group (n = 6) and the TAD group (n = 8) before BAPN diet (p = 0.60 for PWV_sf, p = 0.98 for PWV_dn). In the last measurements after BAPN diet, PWV_dn from the TAD group was lower than that from the control group (p < 0.05), while no significant difference was observed in PWV_sf (p=0.48). PWV_dn increased with the age of the mice for both the control and TAD groups, while the increment of PWV_dn between the last and first measurements was significantly lower in the TAD group (p < 0.05). Such difference was not found in PWV_sf (p = 0.85). These findings indicate that PWV_dn of the abdominal aorta can reflect the arterial stiffness change related to TAD and may be a promising index to monitor the aortic mechanical properties of MS.