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Pulmonary arterial hypertension is a sex-biased condition. The sex bias of PAH may have influenced an increase in the synthesis and use of the long-noncoding RNA X-inactive-specific transcript, which is crucial for X-chromosome transcription and dosage compensation of X-linked genes. The results reveal significant gender-centered differences with respect to EHITSN-induced changes in lung artery remodeling, lung hemodynamics, and a p38/ETS domain with protein/c-Fos signaling, which has ultimately resulted in a more severe female lung PAH phenotype. Cyn A1 expression in female PAH patients' synchronized pulmonary artery endothelial cells in the S and G2/M phases of the cell cycle is higher than those in the G1 and M phases, suggesting functional hyperproliferation. Hence, Xist up-regulation leading to female pulmonary artery endothelial cell sexual dimorphic activity may help provide a greater insight into the genesis of sex bias in PAH.
Source link: https://doi.org/10.1016/j.ajpath.2021.03.009
Pulmonary arterial hypertension affects more women than men, more so women than men, though ill females tend to live longer than males. This sex disparity in PAH has been attributed to the various roles of sex hormones in disease pathology. In comparison, male sex hormone testosterone is linked to reduced longevity in male animals, where it is associated with increased RV mass, volume, and fibrosis. This research paper explores the role of estrogens, related sex hormones, immunological, genetic variation, and diagnostic procedures, as well as the benefits and limitations of current experimental techniques to fill in the gaps in our knowledge of the sex-based variation in PAH development and progression. To investigate gender-based differences in PAH and breast cancer-afflicted male and female pulmonary arteries and design personalized therapies based on patient sex and responsiveness to existing and new drugs, we conclude that we should demonstrate the promise of a new tissue chip-based model imitating PAH-afflicted male and female pulmonary arteries.
Source link: https://doi.org/10.1152/ajplung.00559.2020
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