Identification of Novel Drug Targets for Pulmonary Arterial Hypertension through Integrated Plasma Proteomics - PubMed
6 hours ago
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- #DrugTargets
- #PAH
- Identified plasma proteins causally linked to pulmonary arterial hypertension (PAH) using proteome-wide Mendelian randomization (PWMR).
- Integrated two proteomic GWAS datasets with two PAH GWAS datasets for analysis.
- Prioritized three potential drug targets: CASP10, NOTCH3, and NCAM2.
- Molecular docking predicted strong binding between CASP10 and usnic acid/masoprocol, and NOTCH3 with 2-mercaptobenzothiazole.
- Single-cell RNA sequencing showed CASP10 expression in endothelial/inflammatory cells and NOTCH3 in smooth muscle cells/fibroblasts.
- Phenome-wide association study (PheWAS) found no adverse associations post-FDR correction.
- CASP10 and NOTCH3 highlighted as potential therapeutic targets, with CASP10 prioritized for further evaluation.