{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:48:12Z","timestamp":1783349292867,"version":"3.54.6"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC1300700"],"award-info":[{"award-number":["2016YFC1300700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To study the effect of pharmacological inhibition of epidermal growth factor receptor (EGFR) on intracranial aneurysm (IA) initiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human IA samples were analyzed for the expression of p\u2010EGFR and alpha smooth muscle actin (\u03b1\u2010SMA) by immunofluorescence (IF). Rat models of IA were established to evaluate the ability of the EGFR inhibitor, erlotinib, to attenuate the incidence of IA. We analyzed anterior cerebral artery tissues by pathological and proteomic detection for the expression of p\u2010EGFR and relevant proteins, and vessel casting was used to evaluate the incidence of aneurysms in each group. Rat vascular smooth muscle cells (VSMCs) and endothelial cells were extracted and used to establish an in vitro co\u2010culture model in a flow chamber with or without erlotinib treatment. We determined p\u2010EGFR and relevant protein expression in VSMCs by immunoblotting analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Epidermal growth factor receptor activation was found in human IA vessel walls and rat anterior cerebral artery walls. Treatment with erlotinib markedly attenuated the incidence of IA by inhibiting vascular remodeling and pro\u2010inflammatory transformation of VSMC in rat IA vessel walls. Activation of EGFR in rat VSMCs and phenotypic modulation of rat VSMCs were correlated with the strength of shear stress in vitro, and treatment with erlotinib reduced phenotypic modulation of rat VSMCs. In vitro experiments also revealed that EGFR activation could be induced by TNF\u2010\u03b1 in human brain VSMCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that EGFR plays a critical role in the initiation of IA and that the EGFR inhibitor erlotinib protects rats from IA initiation by regulating phenotypic modulation of VSMCs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13735","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T06:48:02Z","timestamp":1635922082000},"page":"64-76","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Pharmacological inhibition of epidermal growth factor receptor attenuates intracranial aneurysm formation by modulating the phenotype of vascular smooth muscle cells"],"prefix":"10.1111","volume":"28","author":[{"given":"Yin","family":"Luo","sequence":"first","affiliation":[{"name":"Department of 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