| First Author | Gharraee N | Year | 2022 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 322 |
| Issue | 1 | Pages | H44-H56 |
| PubMed ID | 34714692 | Mgi Jnum | J:317123 |
| Mgi Id | MGI:6794109 | Doi | 10.1152/ajpheart.00255.2021 |
| Citation | Gharraee N, et al. (2021) Age and Sex Dependency of Thoracic Aortopathy in a Mouse Model of Marfan Syndrome. Am J Physiol Heart Circ Physiol |
| abstractText | Thoracic aortic aneurysm is one of the manifestations of Marfan syndrome (MFS) that is known to affect men more severely than women. However, the incidence of MFS is similar between men and women. The aim of this study is to show that during pathological aortic dilation, sex-dependent severity of thoracic aortopathy in a mouse model of Marfan syndrome translates into sex-dependent alterations in cells and matrix of the ascending aorta, consequently affecting aortic biomechanics. Fibrillin1 C1041G/+ were used as a mouse model of MFS. Ultrasound measurements from 3-12 months showed increased aortic diameter in Marfan aorta with larger percent increase in diameter for males compared to females. Immunohistochemistry showed decreased contractile smooth muscle cells in Marfan aortic wall compared to healthy aorta, which was accompanied by decreased contractility measured by wire myography. Elastin autofluorescence, second harmonic generation microscopy of collagen fibers and passive biomechanical assessments using myography showed more severe damage to elastin fibers, increased medial fibrosis, and increased stiffness of the aortic wall in MFS males but not females. Male and female heterozygotes showed increased expression of Sca-1-positive adventitial progenitor cells vs. controls at young ages. In agreement with clinical data, Marfan mice demonstrate sex-dependent severity of thoracic aortopathy. It was also shown that aging exacerbates the disease state especially for males. Our findings suggest that female mice are protected from progression of aortic dilation at early ages, leading to a lag in aneurysm growth. |
