GP IIb/IIIa-ICAM-1 Mediated Platelet-Endothelial Adhesion Exacerbates Pulmonary Hypertension
Pulmonary hypertension (PH) patients typically present with a diminished platelet count, but the role of platelets in the development and progression of PH remains unclear.Transcriptomic analysis revealed that platelets from PH patients exhibited an upregulation of genes associated with cellular adhesion, platelet activation, and adhesion. Notably, the hub genes, glycoprotein IIb/IIIa (GP IIb/IIIa), were implicated in mediating platelet-endothelium adhesion through their interaction with intercellular adhesion molecule-1 (ICAM-1) on pulmonary artery endothelial cells, triggering platelet activation and the subsequent release of platelet-derived growth factor BB (PDGF-BB). Overall design: To elucidate the role of platelets in  pulmonary hypertension (PH), we performed RNA sequencing (RNA-seq) on platelets from 8 patients with idiopathic pulmonary arterial hypertension (iPAH) and 5 healthy controls. Our objective was to identify unique transcriptional signatures associated with PH. There were 2920 differentially expressed genes (DEG) in platelets from iPAH patients when compared to healthy controls, with significant changes indicated by |Log2Fold change| > 1 and a false discovery rate < 0.05 . Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses using gene set enrichment analysis (GSEA) highlighted the biological relevance of these DEGs. The most enriched GO and KEGG terms were associated with cellular adhesion, platelet activation, and extracellular matrix remodeling, suggesting heightened platelet adhesion and activation in PH.