{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:11:56Z","timestamp":1784592716710,"version":"3.55.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To study the role of ataxia telangiectasia mutated (ATM) in the platelet-derived growth factor (PDGF)-BB-induced proliferation of pulmonary arterial smooth muscle cells (PASMCs) through reactive oxygen species (ROS) formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary cultures of PASMCs were treated with different concentrations of PDGF-BB or exogenous hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>). 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 H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> were detected under the stimulation of different levels of PDGF-BB by Western blot and dihydroethidium staining.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both the control group and 50 ng\/ml of the PDGF-BB group showed significantly higher levels of phosphorylation ATM compared to other groups (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). With the ATM inhibitor, 50 ng\/ml of the PDGF-BB group showed further increased proliferative level compared to the 10 ng\/ml (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Both the levels of NOX2 and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> showed dose-dependent manners under PDGF-BB stimulation (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). ATM could be activated by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> upon a dose-dependent way, except for the 500 \u03bcM H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> group. Under 200 \u03bcM H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> stimulation, proliferation level decreased significantly (<jats:italic>P<\/jats:italic> &amp;lt; 0.05), while no significant difference was shown with the addition of ATM inhibitor (<jats:italic>P<\/jats:italic> &amp;gt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study first established ROS-induced ATM activation in PDGF-BB-stimulated proliferation of PASMCs. Inhibition of ATM had promoted effects on the proliferation of PASMCs under the excessive levels of PDGF-BB and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. Our study might provide a novel promising target for the treatment of pulmonary arterial hypertension (PAH).<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.942251","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T05:11:30Z","timestamp":1659503490000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Ataxia telangiectasia mutated: The potential negative regulator in platelet-derived growth factor-BB promoted proliferation of pulmonary arterial smooth muscle 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