AUTHOR=Qin Chaoyi , Zan Yiheng , Xie Liang , Liu Hanmin 

TITLE=Ataxia telangiectasia mutated: The potential negative regulator in platelet-derived growth factor-BB promoted proliferation of pulmonary arterial smooth muscle cells

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.942251

DOI=10.3389/fcvm.2022.942251

ISSN=2297-055X

ABSTRACT=Objective: To study the role of ataxia telangiectasia mutated (ATM) in the platelets-derived growth factor (PDGF)-BB-induced proliferation of pulmonary arterial smooth muscle cells (PASMCs) through reactive oxygen species (ROS) formation.
Methods: Primary cultures of PASMCs were treated with different concentrations of PDGF-BB or exogenous H2O2. The activation level of ATM and the proliferation level of PASMCs were measured by immunofluorescence staining and cell counting kit-8, respectively. Moreover, NADPH oxidase 2 (Nox2) and intracellular H2O2 were detected under the stimulation of different levels of PDGF-BB by western blot and dihydroethidium staining. 
Results: Both the control group and 50 ng/mL of PDGF-BB group showed significant higher levels of phosphorylation ATM comparing to other groups (P < 0.05). With the ATM inhibitor, 50 ng/mL of PDGF-BB group showed further increased proliferative level comparing to the 10 ng/mL (P < 0.05). Both levels of Nox2 and H2O2 showed dose-dependent manners under PDGF-BB stimulation (P < 0.05). ATM could be activated by H2O2 upon a dose-dependent way except for the 500 μM H2O2 group. Under 200 μM H2O2 stimulation, proliferation level decreased significantly (P < 0.05) while no significant difference was shown with the addition of ATM inhibitor (P > 0.05).
Conclusion: Our study first established ROS-induced ATM activation in PDGF-BB stimulated proliferation of PASMCs. Inhibition of ATM had promoting effects on the proliferation of PASMCs under excessive level of PDGF-BB and H2O2. Our study might provide a novel promising target for the treatment of PAH.