Abstract 15938: Mice With XX Chromosomes Develop More Severe Hypoxia-Induced Pulmonary Hypertension Than With XY Chromosomes Regardless of Their Gonadal Sex
Rationale: Female rodents have shown protection against development of experimental pulmonary hypertension (PH). Estrogen has been shown to be protective against experimental PH. The precise role of sex hormones and sex chromosomes in this protection is still not clearly understood. The four core genotypes (FCG) model comprises mice in which sex chromosome complement (XX vs. XY) is independent of animal’s gonadal sex. The four genotypes are XX gonadal males or females, and XY gonadal males or females. As females have demonstrated protection against development of experimental PH, we hypothesized that having an extra X chromosome may render protection against the development of PH.
Methods: Inbred C57BL/6 four core genotype mice were gonadectomized at day 75 after birth to eliminate the role of gonadal hormones in adulthood, and 30 days after gonadectomy, were placed in hypoxia chamber (10% oxygen) for three weeks (n=4-5 per group).
Direct cardiac catheterization was performed terminally to assess cardiopulmonary hemodynamics. Masson trichrome staining of lung sections was performed to assess arteriolar hypertrophy and pulmonary fibrosis. Values are expressed as mean?SEM. P<0.05 is considered statistically significant.
Results: Mice with XX-chromosome developed more severe PH than mice with XY chromosome since right ventricular peak systolic pressure (RVPSP) was significantly higher in XX mice than XY mice, regardless of their gonadal sex (44.53±4.82 mm Hg in XX female and 48.96±3.65 in XX male vs. 33.17±2.36 in XY female and 41.57±1.75 in XY male (p<0.01 vs. Female XX and p<0.01 vs. Male XX). FCG mice with an extra X chromosome also had more severe pulmonary vascular remodeling and pulmonary fibrosis compared with the XY mice.
Conclusions: Although females have been shown to be protected against experimental PH, having an extra X chromosome does not offer protection against PH in gonadectomized mice. On the contrary, gonadectomized mice with an extra X-chromosome are more prone to develop hypoxia-induced PH. In short, one X is better than two. This highlights the potential role of sex hormones in protection against hypoxia-induced PH in mice.
Author Disclosures: S. Umar: None. A. Centala: None. A. Iorga: None. S. Sharma: None. A.P. Arnold: None. M. Eghbali: None.
- © 2014 by American Heart Association, Inc.