Author + information
- Yunbin Xiaoa,b,
- Hongyan Penga,b,
- Xuping Qina,b,
- Zhi Chena,b,
- Chenliang Honga,b,
- Xicheng Denga,b and
- Jinwen Luoa,b
Background: The enhanced proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a central pathological component in pulmonary arterial hypertension (PAH). Both the Warburg effect and platelet derived growth factor (PDGF) are involved in the proliferation of PASMCs. However, the mechanism underlying the crosstalk between the Warburg effect and PDGF during PASMC proliferation is still unknown. We hypothesized that PDGF promotes the Warburg effect via activating the phosphatidyl inositol 3-kinase (PI3K) signaling pathway and hypoxia-inducible factor 1-alpha (HIF-1 alpha) in proliferative PASMCs.
Methods: The effect of PDGF on PASMC proliferation was investigated. To determine whether PDGF plays a role in the Warburg effect in these cells, PASMCs were treated with PDGF and then subjected to PDGFR antagonists (sorafenib, imatinib), a Warburg effect inhibitor (2-deoxy-D-glucose) or a PDK1 inhibitor (dichloroacetate). PDGF promoting the Warburg effect via the PI3K signaling pathway and HIF-1 alpha was observed. Cell viability, the presence of metabolites, and metabolic enzyme activities were determined by MTT assay, kit assays, Western blotting and immunofluorescence.
Results: PDGF promoted PASMC proliferation in a dose- and time-dependent manner, which was accompanied by an enhanced Warburg effect. Treatment with PDGFR antagonists, the Warburg effect inhibitor or the PDK1 inhibitor significantly inhibited PI3K signaling activation, HIF-1 alpha expression and PASMC proliferation induced by PDGF, respectively. Furthermore, treatment with PI3K signaling pathway inhibitors remarkably suppressed PDGF-induced PASMC proliferation and the Warburg effect.
Conclusions: The Warburg effect plays a critical role in PDGF-induced PASMC proliferation and is mediated by activation of the PI3K signaling pathway and HIF-1 alpha. In the PAH setting, the Warburg effect may be a new therapeutic target.
Moderated Poster Contributions
Congenital Heart Disease and Pulmonary Hypertension Moderated Poster Theater, Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-9:55 a.m.
Session Title: Bridge From the Basics: Translational Research in Pulmonary Hypertension
Abstract Category: 35. Pulmonary Hypertension and Pulmonary Thrombo-embolic Disease
Presentation Number: 1208M-03
- 2017 American College of Cardiology Foundation