Yasir, a graduate student in Dr. Cassis' laboratory just published a first-author article in the journal "Circulation" (impact factor of 17) with the collaboration of Drs. Cassis, Thatcher, Charnigo, Chen, Blalock and Daugherty.
The work performed and just published is briefly described below:
Abdominal aortic aneurysms (AAAs) are permanent dilations of the abdominal aorta affecting more than 1.1 million people in the US aged 50 to 84. AAA growth is associated with increased likelihood of rupture, with an 85% chance of death after rupture. Male sex is one of the strongest non-modifiable risk factors for AAAs, with estimates ranging from a 2-10 fold greater prevalence in males than females. In this study, we focused on sex chromosome complement as a primary contributor to sexual dimorphism of angiotensin II (AngII)-induced AAAs.
We used a novel murine model that enables dissection of the relative importance of sex hormones versus sex chromosomes to vascular disease development. We hypothesized that an XY sex chromosome complement in phenotypic female mice augments the development and severity of AngII-induced AAAs. Initial studies defined differences in gene expression patterns in abdominal aortas from XX and XY females, demonstrating a preponderance of inflammatory genes exhibiting higher expression levels in aortas from XY females. When XY females were infused with AngII to induce AAA formation, AAA incidence and severity were markedly increased. In the presence of testosterone to mimic the male environment, over 70% of XY females succumbed to aneurysm rupture. These effects were associated with increased oxidative stress and matrix metalloproteinase activity of aortas from XY females.
These results indicate a previously unrecognized role for genes residing on sex chromosomes to influence aortic gene expression patterns and profoundly affect AAA severity. These results may have therapeutic implications for use of sex hormones in aging populations or in transgender individuals. Moreover, these results could be used to identify sex-specific therapeutics for AAAs, a serious vascular disease with no effective therapeutics.