Unraveling the genetic landscape of pulmonary arterial hypertension in Indian patients: A transcriptome study

Pulmonary hypertension (PH) is the abnormal elevation of pressure in the pulmonary vascular system, with various underlying causes. A specific type of PH is pulmonary arterial hypertension (PAH), a severe condition characterized by high pulmonary arterial pressure resulting from structural changes i...

Full description

Saved in:
Bibliographic Details
Published in:Respiratory medicine 2024-09, Vol.231, p.107716, Article 107716
Main Authors: Chauhan, Kirti, Yashavarddhan, M.H., Gogia, Atul, Ranjan, Vivek, Parakh, Ujjawal, Makhija, Aman, Nanavaty, Vishal, Ganguly, Nirmal Kumar, Rana, Rashmi
Format: Article
Language:English
Subjects:
Diagnosis
Pulmonary arterial hypertension
Pulmonary hypertension
Therapeutics
Transcriptomics
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pulmonary hypertension (PH) is the abnormal elevation of pressure in the pulmonary vascular system, with various underlying causes. A specific type of PH is pulmonary arterial hypertension (PAH), a severe condition characterized by high pulmonary arterial pressure resulting from structural changes in distal pulmonary vessels, altered arterial tone, and inflammation. This leads to right ventricular hypertrophy and heart failure. The molecular mechanisms behind PAH are not well understood. This manuscript aims to elucidate these mechanisms using the genetic tool, aiding in diagnosis and treatment selection. In our present study, we have obtained blood samples from both patients with pulmonary arterial hypertension (PAH) and healthy individuals. We conducted a comparative transcriptome analysis to identify genes that are either upregulated or downregulated in PAH patients when compared to the control group. Subsequently, we carried out a validation study focusing on the log2-fold downregulated genes in PAH, employing Quantitative Real-Time PCR for confirmation. Additionally, we quantified the proteins encoded by the validated genes using the ELISA technique. The results of the transcriptome analysis revealed that 97 genes were significantly upregulated, and 6 genes were significantly downregulated. Among these, we chose to focus on and validate only four of the downregulated genes, as they were directly or indirectly associated with the hypertension pathway. We also conducted validation studies for the proteins encoded by these genes, and the results were consistent with those obtained in the transcriptome analysis. In conclusion, the findings of this study indicate that the four validated genes identified in the context of PAH can be further explored as potential targets for both diagnostic and therapeutic applications. •We found out the molecular signatures associated with the pathogenesis of the pulmonary arterial hypertension through transcriptome analysis.•This study made an attempt to find out the familial association of PAH with blood relatives.•In future, the understanding of the selected downregulated marker facilitates better diagnosis.•The article covers chronic comorbidities and clinical parameters of pulmonary arterial hypertension in the Indian population.
ISSN:0954-6111
1532-3064
1532-3064
DOI:10.1016/j.rmed.2024.107716