Sex dimorphism in pulmonary hypertension: the role of the sex chromosomes
File(s)
Published version
Author(s)
Kostyunina, Daria S
McLoughlin, Paul
Type
Journal Article
Abstract
Pulmonary hypertension (PH) is a condition characterised by an abnormal elevation of pulmonary artery pressure caused by an increased pulmonary vascular resistance, frequently leading to right ventricular failure and reduced survival. Marked sexual dimorphism is observed in patients with pulmonary arterial hypertension, a form of pulmonary hypertension with a particularly severe clinical course. The incidence in females is 2–4 times greater than in males, although the disease is less severe in females. We review the contribution of the sex chromosomes to this sex dimorphism highlighting the impact of proteins, microRNAs and long non-coding RNAs encoded on the X and Y chromosomes. These genes are centrally involved in the cellular pathways that cause increased pulmonary vascular resistance including the production of reactive oxygen species, altered metabolism, apoptosis, inflammation, vasoconstriction and vascular remodelling. The interaction with genetic mutations on autosomal genes that cause heritable pulmonary arterial hypertension such as bone morphogenetic protein 2 (BMPR2) are examined. The mechanisms that can lead to differences in the expression of genes located on the X chromosomes between females and males are also reviewed. A better understanding of the mechanisms of sex dimorphism in this disease will contribute to the development of more effective therapies for both women and men.
Date Issued
2021-05-01
Date Acceptance
2021-05-11
Citation
Antioxidants, 2021, 10 (5)
ISSN
2076-3921
Publisher
MDPI AG
Journal / Book Title
Antioxidants
Volume
10
Issue
5
Copyright Statement
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34068984
PII: antiox10050779
Subjects
ACTIVATION
ADENINE-DINUCLEOTIDE PHOSPHATE
apoptosis
ARTERIAL-HYPERTENSION
Biochemistry & Molecular Biology
BMPR2
CAV1
CELL-PROLIFERATION
Chemistry, Medicinal
CLINICAL-FEATURES
EXPRESSION
Food Science & Technology
hypoxia
HYPOXIA
inflammation
Life Sciences & Biomedicine
MECP2 DUPLICATION SYNDROME
metabolism
non-coding RNA
OXIDATIVE STRESS
Pharmacology & Pharmacy
pulmonary arterial hypertension
remodelling
Science & Technology
sex chromosomes
X-INACTIVATION
Publication Status
Published
Coverage Spatial
Switzerland
Article Number
779
Date Publish Online
2021-05-14