GP IIb/IIIa-ICAM-1 Mediated Platelet-Endothelial Adhesion Exacerbates Pulmonary Hypertension

• Published in: American journal of respiratory cell and molecular biology
• Main Authors: Chen, Lingdan, Bai, Qianwen, Tang, Ruidi, Cen, Chunxian, Luo, Qiao, Li, Heying, Lu, Wenju, Liu, Chunli, Ding, Shangwei, Wang, Jian, Hong, Cheng, Wang, Tao
• Format: Journal Article
• Language: English
• Published: 28.02.2025
• ISSN: 1044-1549; 1535-4989; 1535-4989
• DOI: 10.1165/rcmb.2024-0438OC

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. Our research has uncovered that within animal models of PH, platelet depletion or transfusion of platelets from healthy donors reduced pulmonary vascular thickening. In contrast, the transfusion of platelets from PH-affected subjects into healthy animals led to an augmentation of pulmonary vascular thickening. 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 arterial endothelial cells, triggering platelet activation and the subsequent release of platelet-derived growth factor BB (PDGF-BB). This release increased the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). The pharmacological targeting of ICAM-1 has been shown to mitigate PH in a murine model under hypoxic conditions; however, this ameliorative effect was not observed in thrombocytopenic mice under analogous conditions. In summary, the adhesion of platelets to the endothelium, facilitated by GP IIb/IIIa and ICAM-1, exacerbates PH by intensifying the thickening of the pulmonary vascular wall through platelet activation and PDGF-BB secretion.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. Our research has uncovered that within animal models of PH, platelet depletion or transfusion of platelets from healthy donors reduced pulmonary vascular thickening. In contrast, the transfusion of platelets from PH-affected subjects into healthy animals led to an augmentation of pulmonary vascular thickening. 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 arterial endothelial cells, triggering platelet activation and the subsequent release of platelet-derived growth factor BB (PDGF-BB). This release increased the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). The pharmacological targeting of ICAM-1 has been shown to mitigate PH in a murine model under hypoxic conditions; however, this ameliorative effect was not observed in thrombocytopenic mice under analogous conditions. In summary, the adhesion of platelets to the endothelium, facilitated by GP IIb/IIIa and ICAM-1, exacerbates PH by intensifying the thickening of the pulmonary vascular wall through platelet activation and PDGF-BB secretion.