Glycoprotein IIb/IIIa-ICAM-1 mediated platelet-endothelial adhesion aggravates pulmonary hypertension

<bold>Introduction:</bold> Pulmonary hypertension (PH) is a progressive disease characterized by pulmonary vessel remodeling and pulmonary artery pressure elevation. Platelets (PLTs) not only participate in hemostasis and thrombosis, but also contribute to the pathogenesis of various vascular diseases. <bold>Objectives:</bold> To find out whether and how the platelets affect the progression of pulmonary hypertension. <bold>Methods:</bold> RNA sequencing was performed in the platelets from 8 idiopathic pulmonary arterial hypertension (iPAH) and 5 healthy controls to profile the transcriptomic alteration of PH platelets. Platelet and endothelial cell co-culture supernatants was collected to treat pulmonary arterial smooth muscle cells (PASMCs). Co-immunoprecipitation was used to investigate the protein-protein interactions in platelet-endothelium cell adhesion. <bold>Results:</bold> Transcriptome sequencing data showed that genes enriched to platelet adhesion and activation were increased in the platelets from iPAH patients. Protein-protein interaction (PPI) network analysis indicated the hub genes were ITGB3 and ITGA2B. Co-immunoprecipitation shows that platelet Glycoprotein IIb/IIIa (GP IIb/IIIa) formed by ITGB3 and ITGA2B binds to intercellular adhesive molecule-1 (ICAM-1) on pulmonary artery endothelial cells. PH platelet-endothelial cell co-culture conditioned medium increased PASMCs proliferation and migration, which was attenuated by GP IIb/IIIa or ICAM-1 inhibitors. In hypoxia-induced PH mice, ICAM-1 inhibitor reduced pulmonary vascular thickness. <bold>Conclusions:</bold> GP IIb/IIIa and ICAM-1 mediated platelet-endothelium adhesion is increased in the lung from PH, and aggravates pulmonary vascular remodeling of PH.