Association of thoracic spine deformity and cardiovascular disease in a mouse model for Marfan syndrome

AIMS: Cardiovascular manifestations are a major cause of mortality in Marfan syndrome (MFS). Animal models that mimic the syndrome and its clinical variability are instrumental for understanding the genesis and risk factors for cardiovascular disease in MFS. This study used morphological and ultrastructural analysis to the understanding of the development of cardiovascular phenotypes of the the mgΔ(loxPneo) model for MFS. METHODS AND RESULTS: We studied 6-month-old female mice of the 129/Sv background, 6 wild type (WT) and 24 heterozygous animals from the mgΔ(loxPneo) model. Descending thoracic aortic aneurysm and/or dissection (dTAAD) were identified in 75% of the MFS animals, defining two subgroups: MFS with (MFS(+)) and without (MFS(-)) dTAAD. Both subgroups showed increased fragmentation of elastic fibers, predominance of type I collagen surrounding the elastic fiber and fragmentation of interlaminar fibers when compared to WT. However, only MFS animals with spine tortuosity developed aortic aneurysm/dissection. The aorta of MFS(+) animals were more tortuous compared to those of MFS(-) and WT mice, possibly causing perturbations of the luminal blood flow. This was evidenced by the detection of diminished aorta-blood flow in MFS(+). Accordingly, only MFS(+) animals presented a process of concentric cardiac hypertrophy and a significantly decreased ratio of left and right ventricle lumen area. CONCLUSIONS: We show that mgΔ(loxPneo) model mimics the vascular disease observed in MFS patients. Furthermore, the study indicates role of thoracic spine deformity in the development of aorta diseases. We suggest that degradation of support structures of the aortic wall; deficiency in the sustenance of the thoracic vertebrae; and their compression over the adjacent aorta resulting in disturbed blood flow is a triad of factors involved in the genesis of dissection/aneurysm of thoracic aorta.