Y Chromosomal Protection against Pulmonary Arterial Hypertension is not Mediated by Ddx3y
Pulmonary arterial hypertension (PAH) is an incurable vascular disease characterized by elevated pulmonary arterial pressure, vascular remodeling, and lesions leading to right heart failure. It is more prevalent in females than males. In the laboratory, we use a hypoxia model (10% O2) to induce PAH in mice. Our previous data indicate that in the absence of sex hormones mice with a Y chromosome are protected against hypoxic insult as their right ventricular developed pressures (RVDPs), measured by direct catheterization, are lower than that of mice without a Y chromosome. Because four Y chromosomal genes are expressed consistently in lung and heart (Ddx3y, Kdm5d, Uty, Eif2s3y), we hypothesized that one or more of these genes is/are responsible for the protective effect of the Y chromosome. We tested the role of Ddx3y by inducing hypoxia in wild type XX mice with and without a Ddx3y transgene. Our results showed no significant difference in the severity of PAH between the two groups. This result allows us to test for the roles of other candidates.