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


Autoři: Rodrigo Barbosa de Souza aff001;  Luis Ernesto Farinha-Arcieri aff001;  Marcia Helena Braga Catroxo aff002;  Ana Maria Cristina Rebelo Pinto da Fonseca Martins aff002;  Roberto Carlos Tedesco aff003;  Luis Garcia Alonso aff003;  Ivan Hong Jun Koh aff004;  Lygia V. Pereira aff001
Působiště autorů: University of São Paulo, Department of Genetics and Evolutionary Biology, São Paulo, SP, Brazil aff001;  Biologic Institute of São Paulo, Department of Electron Microscopy, São Paulo, SP, Brazil aff002;  Federal University of São Paulo, Department of Morphological and Genetics, São Paulo, SP, Brazil aff003;  Federal University of São Paulo, Department of Surgery, São Paulo, SP, Brazil aff004
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224581

Souhrn

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 mgΔloxPneo 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 mgΔloxPneo 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 mgΔloxPneo 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.

Klíčová slova:

Aneurysms – Aorta – Blood flow – Cardiac ventricles – Collagens – Mouse models – Spine


Zdroje

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Článek vyšel v časopise

PLOS One


2019 Číslo 11