Abstract Number: VPB0902
Meeting: ISTH 2022 Congress
Background: Metabolic reprogramming is a hallmark of pulmonary arterial hypertension. Platelet activation have been implicated in Pulmonary Arterial Hypertension (PAH). Whereas the role of platelet in the pathogenesis of PAH remains unclear.
Aims: To explore the effect of platelet derived TGF-β1 on pulmonary arterial smooth muscle cells proliferation, migration, and aerobic glycolysis.
Methods: We explored the platelet function of SU5416/hypoxia mice and MCT injected rats PAH model. Then we investigated pulmonary arterial smooth muscle cells aerobic glycolysis after treated with platelet supernatant, TGF β RI, PKM2 and other antagonists were applied to identify the underlying mechanism. In addition, platelet specific deletion TGFβ1 mice were exposed to chronic hypoxia and SU5416. Cardiopulmonary hemodynamics, vascular remodeling and aerobic glycolysis of PASMC was determined.
Results: We demonstrate that platelet released TGFβ1 enhances the aerobic glycolysis of pulmonary arterial smooth muscle cells after platelet activation via increasing PKM2 expression. Mechanistically, platelet derived TGFβ1 regulates PKM2 expression through mTOR/c-Myc/PTBP1-hnRNPA1 pathway. Platelet TGFβ1 deficiency mice are significantly protected from SU5416 plus chronic hypoxia induced PAH, including attenuated increases in right ventricular systolic pressure and less pulmonary vascular remodeling. Also, in Pf4 cre+ Tgfb1 fl/fl mice PAMSCs showed lower glycolysis capacity and their PKM2 expression decreased.
Conclusion(s): Our data demonstrate that TGFβ1 released by platelet contributes to the pathogenesis of PAH and further highlights the role of platelet in PAH.
To cite this abstract in AMA style:Ming Z, Zhu Y, Gong X, Lu M, Zeng X, Gao J, Guo Y, Liu L, Ma R. Deletion of TGF-β1 on platelets attenuates pulmonary arterial hypertension by enhancing aerobic glycolysis of pulmonary arterial smooth muscle cell [abstract]. https://abstracts.isth.org/abstract/deletion-of-tgf-%ce%b21-on-platelets-attenuates-pulmonary-arterial-hypertension-by-enhancing-aerobic-glycolysis-of-pulmonary-arterial-smooth-muscle-cell/. Accessed February 28, 2024.
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