Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response
Small-diameter vascular grafts (diameter <6 mm) are in high demand in clinical practice. Neointimal hyperplasia, a common complication after implantation of small-diameter vascular grafts, is one of the common causes of graft failure. Modulation of local inflammatory responses is a promising...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-12-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.1066266/full |
| _version_ | 1828114172975513600 |
|---|---|
| author | Xinlong Xie Xinlong Xie Qiying Wu Yuhong Liu Chunyang Chen Zeguo Chen Chao Xie Mingzhe Song Zhenlin Jiang Xiaoke Qi Sixi Liu Zhenjie Tang Zhenjie Tang Zhongshi Wu Zhongshi Wu |
| author_facet | Xinlong Xie Xinlong Xie Qiying Wu Yuhong Liu Chunyang Chen Zeguo Chen Chao Xie Mingzhe Song Zhenlin Jiang Xiaoke Qi Sixi Liu Zhenjie Tang Zhenjie Tang Zhongshi Wu Zhongshi Wu |
| author_sort | Xinlong Xie |
| collection | DOAJ |
| description | Small-diameter vascular grafts (diameter <6 mm) are in high demand in clinical practice. Neointimal hyperplasia, a common complication after implantation of small-diameter vascular grafts, is one of the common causes of graft failure. Modulation of local inflammatory responses is a promising strategy to attenuates neointimal hyperplasia. Vascular endothelial growth factor (VEGF) is an angiogenesis stimulator that also induces macrophage polarization and modulates inflammatory responses. In the present study, we evaluated the effect of VEGF on the neointima hyperplasia and local inflammatory responses of decellularized vascular grafts. In the presence of rhVEGF-165 in RAW264.6 macrophage culture, rhVEGF-165 induces RAW264.6 macrophage polarization to M2 phenotype. Decellularized bovine internal mammary arteries were implanted into the subcutaneous and infrarenal abdominal aorta of New Zealand rabbits, with rhVEGF-165 applied locally to the adventitial of the grafts. The vascular grafts were removed en-bloc and submitted to histological and immunofluorescence analyses on days 7 and 28 following implantation. The thickness of the fibrous capsule and neointima was thinner in the VEGF group than that in the control group. In the immunofluorescence analysis, the number of M2 macrophages and the ratio of M2/M1 macrophages in vascular grafts in the VEGF group were higher than those in the control group, and the proinflammatory factor IL-1 was expressed less than in the control group, but the anti-inflammatory factor IL-10 was expressed more. In conclusion, local VEGF administration attenuates neointimal hyperplasia in decellularized small-diameter vascular grafts by inducing macrophage M2 polarization and modulating the inflammatory response. |
| first_indexed | 2024-04-11T12:20:39Z |
| format | Article |
| id | doaj.art-991a0597ba994a90aa92b67f6bc9981d |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-11T12:20:39Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-991a0597ba994a90aa92b67f6bc9981d2022-12-22T04:24:06ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-12-011010.3389/fbioe.2022.10662661066266Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory responseXinlong Xie0Xinlong Xie1Qiying Wu2Yuhong Liu3Chunyang Chen4Zeguo Chen5Chao Xie6Mingzhe Song7Zhenlin Jiang8Xiaoke Qi9Sixi Liu10Zhenjie Tang11Zhenjie Tang12Zhongshi Wu13Zhongshi Wu14Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Cardiothoracic Surgery, The First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaEngineering Laboratory of Hunan Province for Cardiovascular Biomaterials, Changsha, Hunan, ChinaDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaEngineering Laboratory of Hunan Province for Cardiovascular Biomaterials, Changsha, Hunan, ChinaSmall-diameter vascular grafts (diameter <6 mm) are in high demand in clinical practice. Neointimal hyperplasia, a common complication after implantation of small-diameter vascular grafts, is one of the common causes of graft failure. Modulation of local inflammatory responses is a promising strategy to attenuates neointimal hyperplasia. Vascular endothelial growth factor (VEGF) is an angiogenesis stimulator that also induces macrophage polarization and modulates inflammatory responses. In the present study, we evaluated the effect of VEGF on the neointima hyperplasia and local inflammatory responses of decellularized vascular grafts. In the presence of rhVEGF-165 in RAW264.6 macrophage culture, rhVEGF-165 induces RAW264.6 macrophage polarization to M2 phenotype. Decellularized bovine internal mammary arteries were implanted into the subcutaneous and infrarenal abdominal aorta of New Zealand rabbits, with rhVEGF-165 applied locally to the adventitial of the grafts. The vascular grafts were removed en-bloc and submitted to histological and immunofluorescence analyses on days 7 and 28 following implantation. The thickness of the fibrous capsule and neointima was thinner in the VEGF group than that in the control group. In the immunofluorescence analysis, the number of M2 macrophages and the ratio of M2/M1 macrophages in vascular grafts in the VEGF group were higher than those in the control group, and the proinflammatory factor IL-1 was expressed less than in the control group, but the anti-inflammatory factor IL-10 was expressed more. In conclusion, local VEGF administration attenuates neointimal hyperplasia in decellularized small-diameter vascular grafts by inducing macrophage M2 polarization and modulating the inflammatory response.https://www.frontiersin.org/articles/10.3389/fbioe.2022.1066266/fullneointimal hyperplasiamacrophagesvascular endothelial growth factorsmall-diameter vascular graftdecellularized |
| spellingShingle | Xinlong Xie Xinlong Xie Qiying Wu Yuhong Liu Chunyang Chen Zeguo Chen Chao Xie Mingzhe Song Zhenlin Jiang Xiaoke Qi Sixi Liu Zhenjie Tang Zhenjie Tang Zhongshi Wu Zhongshi Wu Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response Frontiers in Bioengineering and Biotechnology neointimal hyperplasia macrophages vascular endothelial growth factor small-diameter vascular graft decellularized |
| title | Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response |
| title_full | Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response |
| title_fullStr | Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response |
| title_full_unstemmed | Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response |
| title_short | Vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small-diameter vascular grafts by modulating the local inflammatory response |
| title_sort | vascular endothelial growth factor attenuates neointimal hyperplasia of decellularized small diameter vascular grafts by modulating the local inflammatory response |
| topic | neointimal hyperplasia macrophages vascular endothelial growth factor small-diameter vascular graft decellularized |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.1066266/full |
| work_keys_str_mv | AT xinlongxie vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT xinlongxie vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT qiyingwu vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT yuhongliu vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT chunyangchen vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT zeguochen vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT chaoxie vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT mingzhesong vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT zhenlinjiang vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT xiaokeqi vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT sixiliu vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT zhenjietang vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT zhenjietang vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT zhongshiwu vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse AT zhongshiwu vascularendothelialgrowthfactorattenuatesneointimalhyperplasiaofdecellularizedsmalldiametervasculargraftsbymodulatingthelocalinflammatoryresponse |