{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:30:01Z","timestamp":1783344601473,"version":"3.54.6"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Moyamoya disease (MMD) is a unique cerebrovascular occlusive disease characterized by progressive steno-occlusion within the terminal segment of the internal carotid artery. However, good collaterals from an external carotid artery are essential to compensate for the ischemia in moyamoya disease. This study aimed to investigate the transforming growth factor-beta 1 (TGF\u03b21) in plasma as a potential biomarker for predicting collateral formation in ischemic MMD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The transcriptome profile downloaded from Gene Expression Omnibus (GEO) was used to analyze the differential expression of genes between the ischemic MMD and the control groups. We prospectively recruited 23 consecutive patients with ischemic MMD that was diagnosed <jats:italic>via<\/jats:italic> digital subtraction angiography (DSA). Nine patients with intracranial aneurysms and four healthy people served as controls. The collaterals from the external carotid artery were examined using DSA. We evaluated whether the collateral formation was associated with TGF\u03b21 in patients with ischemic MMD. Western blot, RT-qPCR, ELISA, and tube formation assay were used to explore the relationship between TGF\u03b21 and angiogenesis, as well as the potential mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mRNA levels of TGF\u03b21 were upregulated in the patients with ischemic MMD. The plasma TGF\u03b21 levels were higher in the patients with ischemic MMD than in the aneurysm and healthy patients (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). The collateral formation group has higher levels of serum TGF\u03b21 than the non-collateral formation group (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). The levels of vascular endothelial growth factor (VEGF) are positively correlated with TGF\u03b21 levels in the plasma (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> = 0.6115; <jats:italic>p<\/jats:italic> &amp;lt; 0.0001). TGF\u03b21 regulates VEGF expression <jats:italic>via<\/jats:italic> the activation of the TGF\u03b2 pathway within HUVEC cells, as well as TGF\u03b21 stimulating HUVEC cells to secrete VEGF into the cell culture media. An <jats:italic>in vitro<\/jats:italic> assay revealed that TGF\u03b21 promotes angiogenesis within the endothelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that TGF\u03b21 plays a vital role in promoting collateral formation by upregulating VEGF expression in ischemic MMD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.899470","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T07:53:20Z","timestamp":1657180400000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["TGF\u03b21 as a Predictive Biomarker for Collateral Formation Within Ischemic Moyamoya Disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Yuanbing","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1056\/NEJMra0804622","article-title":"Moyamoya 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