Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissue
Abstract Background Over half of patients with chronically ischaemic cerebrovascular disease (CICD) exhibit poor revascularization potential. Tie2-expressing monocytes/macrophages (TEMs) have been reported to promote angiogenesis in tumour tissue; however, whether TEMs promote angiogenesis in chroni...
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BMC
2025-05-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-025-01401-1 |
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| author | Chuyang Tai Cong Ling Yang Yang Baoyu Zhang Jun Sun Ni Mo Tao Sun Lixin Huang Cian Yao Hui Wang Chuan Chen |
| author_facet | Chuyang Tai Cong Ling Yang Yang Baoyu Zhang Jun Sun Ni Mo Tao Sun Lixin Huang Cian Yao Hui Wang Chuan Chen |
| author_sort | Chuyang Tai |
| collection | DOAJ |
| description | Abstract Background Over half of patients with chronically ischaemic cerebrovascular disease (CICD) exhibit poor revascularization potential. Tie2-expressing monocytes/macrophages (TEMs) have been reported to promote angiogenesis in tumour tissue; however, whether TEMs promote angiogenesis in chronically ischaemic brain tissue (CIBT) and the regulatory mechanism through which TEMs are recruited to CIBT remain unclear. Methods We first analysed the proportion of TEMs in blood from the internal jugular veins (IJVs) of CICD patients and then isolated TEMs for coculture with human umbilical vein endothelial cells (HUVECs) and for intraventricular injection into nude mice to explore the proangiogenic effects of TEMs in CIBT. Then, molecular biology experiments were performed to verify the upstream regulatory mechanism of the ANGPT2-Tie2 axis, and cell transfection experiments were conducted to confirm the regulatory effects of the detected pathway on Tie2 receptors on the endothelial cell surface. Additionally, a 2-vessel occlusion plus encephalomyosynangiosis rat model was established to confirm the recruitment mechanism of TEMs in CIBT and their ability to improve cerebral blood perfusion (CBP) and cognitive function. Results The proportion of TEMs from the IJV blood of CICD patients significantly increased, especially in patients who exhibited Matsushima Grade-A revascularization. The viability of HUVECs cocultured with TEMs was significantly increased, and CBP and the expression of CD31 in the CIBT of nude mice treated with TEMs were significantly increased. The above increases were positively correlated with the concentration of TEMs used for coculture and intraventricular injection. Moreover, molecular biology experiments indicated that miR-126-5p can directly bind to the 3'UTR of TRPS1 mRNA and that TRPS1 can directly bind to the promoter of Angpt2. HUVECs transfected with miR-126-5p mimics presented significantly decreased TRPS1 expression, a reduced pTie2/Tie2 ratio, increased ANGPT2 expression, and increased cell viability. Finally, significantly increased TEMs infiltration, downregulated TRPS1 expression, and upregulated ANGPT2, CD31, VEGFA, and IGF1 expression were detected in the CIBT of the rats transfected with the miR-126-5p agomir, accompanied by significant improvements in CBP and cognitive function. Conclusions TEMs promote angiogenesis in CIBT through a paracrine mechanism, and the recruitment of TEMs to CIBT is regulated by the miR-126-5p/TRPS1/ANGPT2 pathway. |
| format | Article |
| id | doaj-art-fa77178dc1784026812d52196ba383db |
| institution | DOAJ |
| issn | 2045-3701 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Cell & Bioscience |
| spelling | doaj-art-fa77178dc1784026812d52196ba383db2025-08-20T03:08:44ZengBMCCell & Bioscience2045-37012025-05-0115112410.1186/s13578-025-01401-1Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissueChuyang Tai0Cong Ling1Yang Yang2Baoyu Zhang3Jun Sun4Ni Mo5Tao Sun6Lixin Huang7Cian Yao8Hui Wang9Chuan Chen10Department of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Radiology, Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen UniversityDepartment of Neurosurgery, Third Affiliated Hospital of Sun Yat-Sen UniversityAbstract Background Over half of patients with chronically ischaemic cerebrovascular disease (CICD) exhibit poor revascularization potential. Tie2-expressing monocytes/macrophages (TEMs) have been reported to promote angiogenesis in tumour tissue; however, whether TEMs promote angiogenesis in chronically ischaemic brain tissue (CIBT) and the regulatory mechanism through which TEMs are recruited to CIBT remain unclear. Methods We first analysed the proportion of TEMs in blood from the internal jugular veins (IJVs) of CICD patients and then isolated TEMs for coculture with human umbilical vein endothelial cells (HUVECs) and for intraventricular injection into nude mice to explore the proangiogenic effects of TEMs in CIBT. Then, molecular biology experiments were performed to verify the upstream regulatory mechanism of the ANGPT2-Tie2 axis, and cell transfection experiments were conducted to confirm the regulatory effects of the detected pathway on Tie2 receptors on the endothelial cell surface. Additionally, a 2-vessel occlusion plus encephalomyosynangiosis rat model was established to confirm the recruitment mechanism of TEMs in CIBT and their ability to improve cerebral blood perfusion (CBP) and cognitive function. Results The proportion of TEMs from the IJV blood of CICD patients significantly increased, especially in patients who exhibited Matsushima Grade-A revascularization. The viability of HUVECs cocultured with TEMs was significantly increased, and CBP and the expression of CD31 in the CIBT of nude mice treated with TEMs were significantly increased. The above increases were positively correlated with the concentration of TEMs used for coculture and intraventricular injection. Moreover, molecular biology experiments indicated that miR-126-5p can directly bind to the 3'UTR of TRPS1 mRNA and that TRPS1 can directly bind to the promoter of Angpt2. HUVECs transfected with miR-126-5p mimics presented significantly decreased TRPS1 expression, a reduced pTie2/Tie2 ratio, increased ANGPT2 expression, and increased cell viability. Finally, significantly increased TEMs infiltration, downregulated TRPS1 expression, and upregulated ANGPT2, CD31, VEGFA, and IGF1 expression were detected in the CIBT of the rats transfected with the miR-126-5p agomir, accompanied by significant improvements in CBP and cognitive function. Conclusions TEMs promote angiogenesis in CIBT through a paracrine mechanism, and the recruitment of TEMs to CIBT is regulated by the miR-126-5p/TRPS1/ANGPT2 pathway.https://doi.org/10.1186/s13578-025-01401-1AngiogenesisChronically ischaemic cerebrovascular diseaseEncephalomyosynangiosisIschaemic strokeTie2-expressing monocytes/macrophages |
| spellingShingle | Chuyang Tai Cong Ling Yang Yang Baoyu Zhang Jun Sun Ni Mo Tao Sun Lixin Huang Cian Yao Hui Wang Chuan Chen Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissue Cell & Bioscience Angiogenesis Chronically ischaemic cerebrovascular disease Encephalomyosynangiosis Ischaemic stroke Tie2-expressing monocytes/macrophages |
| title | Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissue |
| title_full | Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissue |
| title_fullStr | Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissue |
| title_full_unstemmed | Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissue |
| title_short | Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissue |
| title_sort | tie2 expressing monocytes macrophages promote angiogenesis in chronically ischaemic brain tissue |
| topic | Angiogenesis Chronically ischaemic cerebrovascular disease Encephalomyosynangiosis Ischaemic stroke Tie2-expressing monocytes/macrophages |
| url | https://doi.org/10.1186/s13578-025-01401-1 |
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