Related Experiment Video
Updated: Sep 28, 2025
Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Text Mining-Based Drug Discovery for Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
Jiang-Shan Tan1, Song Hu1, Ting-Ting Guo1
1Key Laboratory of Pulmonary Vascular Medicine, State Key Laboratory of Cardiovascular Disease, Center for Respiratory and Pulmonary Vascular Diseases, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Insights
Researchers identified 13 potential drugs for connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). These drugs target six key genes, offering new therapeutic possibilities for patients with CTD-PAH.
Area of Science:
- Biomedical Informatics
- Pharmacology
- Pulmonary Medicine
Background:
- Current treatments for connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) have limited efficacy.
- There is a critical need for novel therapeutic agents for CTD-PAH.
Purpose of the Study:
- To identify potential novel drug candidates for CTD-PAH using a text mining and bioinformatics approach.
- To explore existing drugs that could be repurposed for CTD-PAH treatment.
Main Methods:
- Text mining was employed to identify genes associated with connective tissue disease (CTD) and pulmonary arterial hypertension (PAH).
- Functional enrichment analysis and protein-protein interaction network analysis were performed on overlapping genes.
- The Drug Gene Interaction database was utilized to identify potential therapeutic drugs targeting identified genes.
Main Results:
- A total of 179 CTD- and PAH-related genes were identified, leading to 20 genes involved in six key pathways.
- Thirteen candidate drugs targeting these six genes were selected, with 12 having FDA approval for other indications.
- Identified drug targets include IL-6, IL-1β, MMP9, VEGFA, TGFB1, and EGFR.
Conclusions:
- This study identified 13 drugs with potential therapeutic benefits for CTD-PAH.
- These drugs target critical genes involved in the pathophysiology of CTD-PAH.
- The findings suggest a promising avenue for developing new treatments for CTD-PAH.
Abstract:
Background: The current medical treatments for connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) do not show favorable efficiency for all patients, and identification of novel drugs is desired. Methods: Text mining was performed to obtain CTD- and PAH-related gene sets, and the intersection of the two gene sets was analyzed for functional enrichment through DAVID. The protein-protein interaction network of the overlapping genes and the significant gene modules were determined using STRING. The enriched candidate genes were further analyzed by Drug Gene Interaction database to identify drugs with potential therapeutic effects on CTD-PAH. Results: Based on text mining analysis, 179 genes related to CTD and PAH were identified. Through enrichment analysis of the genes, 20 genes representing six pathways were obtained. To further narrow the scope of potential existing drugs, we selected targeted drugs with a Query Score ≥5 and Interaction Score ≥1. Finally, 13 drugs targeting the six genes were selected as candidate drugs, which were divided into four drug-gene interaction types, and 12 of them had initial drug indications approved by the FDA. The potential gene targets of the drugs on this list are IL-6 (one drug) and IL-1β (two drugs), MMP9 (one drug), VEGFA (three drugs), TGFB1 (one drug), and EGFR (five drugs). These drugs might be used to treat CTD-PAH. Conclusion: We identified 13 drugs targeting six genes that may have potential therapeutic effects on CTD-PAH.
More Related Videos
09:23Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension
Published on: February 11, 2017
05:47Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
Related Concept Videos
01:22Connective Tissue Cell Types
Fat cells (adipocytes), smooth muscle cells (myoblasts), and bone cells (osteoblasts) are some connective tissue cell types. Some immune system cells...
01:30Pulmonary Hypertension: Classification and Pathogenesis
There are various classifications for PH, each relating to different underlying causes and also...
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:28Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...