Abstract 16433: Protection Conferred by Y-chromosome Against Hypoxia-induced Pulmonary Hypertension is Not Due to Ddx3y Gene
Introduction: Pulmonary hypertension (PH) is a chronic pulmonary vascular disease characterized by elevated pulmonary arterial pressures and vascular remodelling leading to right ventricular failure. It is 4 times more likely to occur in females than males. The reasons for the female predominance or male protection are still not fully elucidated. Our previous work showed that in gonadectomized (GDX) Four Core Genotypes (FCG) mice (XX and XY males, XX and XY females, C57BL6/J), XY mice having a Y-chromosome (XYM, XYF) develop less severe PH than the XX mice lacking a Y-chromosome (XXM, XXF).
Hypothesis: Protection against hypoxia-induced PH in gonadectomized mice is due to the presence of Y-chromosome and not due to the number of X-chromosomes. We also examined the role of a Y-chromosome gene Ddx3y, a cellular growth suppressor expressed consistently in the lungs and heart in protection against PH.
Methods: Here we used GDX XY* C57BL/6J mouse model which allows us to have male mice with XY or XXY and female mice with XX or XO genotypes (n=5/group). In addition we also used XX female mice with and without a transgenic copy of Y-chromosome gene Ddx3y (n=10/group). Mice were gonadectomized at day-75 and 4-weeks after gonadectomy, were exposed to hypoxia (10% O2) for 3-weeks. RVSP was measured through direct catheterization.
Results: In the GDX XY* model, right ventricular systolic pressure (RVSP) in mice with Y-chromosome (XY=33.5±0.6, XXY=32±2mmHg) was significantly lower than that of mice without a Y-chromosome (XO=38.7±2, XX=41.5±3.8, P<0.05). We concluded that presence of Y-chromosome confers protection against PH in GDX mice. Four Y-chromosome genes are expressed consistently in the lungs and heart (Ddx3y, Kdm5d, Uty, Eif2x3y) and are thus candidate protective genes. We did not find a significant difference between the RVSP of XX mice with or without a transgenic copy of Ddx3y.
Conclusions: We conclude that Y-chromosome confers protection against hypoxia-induced PH in GDX mice which is not due to Ddx3y gene. Next we plan to investigate effects of the other Y-chromosome candidate genes Kdm5d, Uty, and Eif2x3y.
Author Disclosures: S. Umar: None. M. Barseghyan: None. A. Centala: None. Y. Itoh: None. R. Mackie: None. A.P. Arnold: None. M. Eghbali: None.
- © 2015 by American Heart Association, Inc.