VPB0902 - Deletion of TGF-β1 on platelets attenuates pulmonary arterial hypertension by enhancing aerobic glycolysis of pulmonary arterial smooth muscle cell

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Zhang-Yin Ming, MA PhD MD

faculty
Tongji medical colledge, Huazhong university of science & technology
Wuhan, Hubei, China (People's Republic)

Co-Author(s)

YZ

Ying Zhu

PhD
Department of Pharmacology, Tongji Medical College Of Huazhong University Of Science And Technology
Wuhan, Hubei, China (People's Republic)
XG

Xue Gong

graduate student
Tongji medical colledge, Huazhong university of science & technology
Wuhan, Hubei, China (People's Republic)
ML

Meng Lu

PhD student
Tongji medical colledge, Huazhong university of science & technology
Wuhan, Hebei, China (People's Republic)
XZ

Xiang-bing Zeng

PhD student
Tongji medical colledge, Huazhong university of science & technology
Wuhan, Hubei, China (People's Republic)
JG

Jia-Hui Gao

PhD student
Tongji medical colledge, Huazhong university of science & technology
Wuhan, Hubei, China (People's Republic)
YG

Ya-Wei Guo

PhD student
Tongji medical colledge, Huazhong university of science & technology
Wuhan, Hubei, China (People's Republic)
LL

Lu-Man Liu

MD
Department of Pharmacology, Tongji Medical College Of Huazhong University Of Science And Technology
Wuhan, Hubei, China (People's Republic)
RM

Rong Ma

faculty
Tongji medical colledge, Huazhong university of science & technology
Wuhan, Hubei, China (People's Republic)

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.