Platelet activation contributes to hypoxia-induced inflammation

Cassidy Delaney, Pavel Davizon-Castillo, Ayed Allawzi, Janelle Posey, Aneta Gandjeva, Keith Neeves, Rubin M. Tuder, Jorge Di Paola, Kurt R. Stenmark, Eva S. Nozik

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Inflammation is central to the pathogenesis of pulmonary vascular remodeling and pulmonary hypertension (PH). Inflammation precedes remodeling in preclinical models, thus supporting the concept that changes in immunity drive remodeling in PH. Platelets are recognized as mediators of inflammation, but whether platelets contribute to hypoxia-driven inflammation has not been studied. We utilized a murine hypoxia model to test the hypothesis that platelets drive hypoxia-induced inflammation. We evaluated male and female 9-wk-old normoxic and hypoxic mice and in selected experiments included hypoxic thrombocytopenic mice. Thrombocytopenic mice were generated with an anti-GP1bα rat IgG antibody. We also performed immunostaining of lung sections from failed donor controls and patients with idiopathic pulmonary arterial hypertension. We found that platelets are increased in the lungs of hypoxic mice and hypoxia induces platelet activation. Platelet depletion prevents hypoxia-driven increases in the proinflammatory chemokines CXCL4 and CCL5 and attenuates hypoxia-induced increase in plasma CSF-2. Pulmonary interstitial macrophages are increased in the lungs of hypoxic mice; this increase is prevented in thrombocytopenic mice. To determine the potential relevance to human disease, lung sections from donors and patients with advanced idiopathic pulmonary arterial hypertension (iPAH) were immunostained for the platelet-specific protein CD41. We observed iPAH lungs had a two-fold increase in CD41, compared with controls. Our data provide evidence that the platelet count is increased in the lungs and activated in mice with hypoxia-induced inflammation and provides rationale for the further study of the potential contribution of platelets to inflammatory mediated vascular remodeling and PH.

Original languageEnglish
Pages (from-to)L413-L421
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number3
StatePublished - Mar 2021


  • Hypertension
  • Hypoxia
  • Inflammation
  • Platelet
  • Pulmonary hypertension


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