Pulmonary arterial hypertension (PAH) is a life-threatening disease that affects the pulmonary vasculature and ultimately leads to right heart failure. In recent years, much research has been conducted to understand the underlying mechanisms of this disease. A recent study published in Scientific Reports has shed new light on the role of GATA6 in coordinate cross-talk between BMP10 and oxidative stress axis in the development of PAH. This article will explore the findings of this study and their implications for the future diagnosis and treatment of PAH.
This content discusses the use of human tissues and cell cultures in experimental procedures. The experiments were conducted in accordance with the principles outlined in the Declaration of Helsinki, and protocols approved by the University of Pittsburgh Institutional Review Board and the Committee for Oversight of Research and Clinical Training Involving Decedents.
Lung tissue specimens were obtained from patients with Pulmonary Arterial Hypertension (PAH) and non-diseased (control) donors. The early-passage distal human PASMC and PAECs from non-diseased subjects or patients with PAH were provided by the University of Pittsburgh Cell Processing Core and Pulmonary Hypertension Breakthrough Initiative (PHBI) in accordance with PHBI, IRB, and CORID protocols. Before tissue collection, an informed consent was obtained from all subjects and/or their legal guardian(s).
Control PAECs were purchased from Lonza and cultured in complete endothelial growth medium. The experiments were performed in accordance with the protocols approved by the Boston University Institutional Animal Care and Use Committee, and the investigation conformed to the Guide for the Care and Use of Laboratory Animals.
Gata6 CKO mice were generated by breeding Gata6 flox/flox mice with mice expressing the Cre recombinase under the control of the endothelial-specific VE-cadherin promoter. DMF intraperitoneal injections were performed daily for three weeks, and the control group was injected with an equal volume of vehicle/DMSO solution.
Two different methods were used to isolate mouse endothelial cells (ECs), and BMP9 and BMP10 were purchased from PeproTech. Immunohistochemical analysis was performed on 4% paraformaldehyde-fixed, paraffin-embedded 5-μm sections after dewaxing and heat antigen retrieval.
RNA was isolated and purified from mouse total lungs, mouse lung ECs, human PAECs, and human VSMCs, and quantitative RT-PCR was performed. Microarray analysis was performed at The Boston University Microarray Core Facility.
Antioxidant enzyme activity measurements were conducted using commercial kits. The experiments provide insight into various aspects of biology and show the importance of following ethical and regulatory protocols during experimental procedures.
In conclusion, this article sheds light on the important role played by GATA6 in pulmonary arterial hypertension. The study suggests that GATA6 coordinates cross-talk between BMP10 and the oxidative stress axis, which could serve as a potential therapeutic target in the treatment of PAH. The findings provide new insights into the molecular mechanisms underlying PAH, and highlight the importance of further research in this field. Overall, this study is a significant step in the direction of developing effective treatments for this devastating disease.
