2. Academic Validation
  3. GP IIb/IIIa-ICAM-1 Mediated Platelet-Endothelial Adhesion Exacerbates Pulmonary Hypertension

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

  • Am J Respir Cell Mol Biol. 2025 Feb 28. doi: 10.1165/rcmb.2024-0438OC.
Lingdan Chen 1,  Qianwen Bai 1,  Ruidi Tang 1,  Chunxian Cen 2,  Qiao Luo 3,  Heying Li 4,  Wenju Lu 5,  Chunli Liu 6,  Shangwei Ding 7,  Jian Wang 3,  Cheng Hong 8,  Tao Wang 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 2 State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 3 State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, GuangDong, China.
  • 4 State Key Laboratory of Respiratory Disease, Guangdong Laboratory of Computational Biomedicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, GuangDong, China.
  • 5 First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China.
  • 6 Guangzhou Institute of Respiratory Disease, Respiratory Medicine, Guangzhou, Guangdong, China.
  • 7 First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 8 Guangzhou Medical University The First Associated Hospital, Guangzhou Institute of Respiratory Diseases, Guangzhou, China.
  • 9 Guangzhou Institute of Respiratory Disease, Respiratory Medicine, Guangzhou, Guangdong, China; taowang@gzhmu.edu.cn.
PMID: 40019848 DOI: 10.1165/rcmb.2024-0438OC
Abstract

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.

Keywords

Glycoprotein IIb/IIIa; Platelet-Derived Growth Factor BB; Pulmonary hypertension; intercellular adhesion molecule-1; platelet-endothelium interactions.

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