Pub Date : 2019-01-03eCollection Date: 2019-01-01DOI: 10.1530/VB-18-0005
Paolo Madeddu
The year 2018 marked the 110th anniversary of Goldmann’s discovery that vascularization is an active process in tissues1 and the 50th anniversary of the concomitant reports from Greenblatt and Shubik2 and Ehrmann and Knoth3 that soluble morphogenic factors are required for cancer angiogenesis. Many other radically transformative paradigms have been introduced in the last decades. To name a few, the molecular search for the identity of master regulators of vascular tone led to the discovery of the Endothelium-Derived Relaxing Factor (EDRF; i.e., NO4), while clinically inspired investigations led to the recognition of the pathophysiological relevance of neoangiogenesis in cancer and tissue healing. This brought about the proposal of blocking angiogenesis to halt tumor growth and stimulating angiogenesis to treat myocardial ischemia and heart failure5-7.
{"title":"Why is a new journal dedicated to vascular biology required?","authors":"Paolo Madeddu","doi":"10.1530/VB-18-0005","DOIUrl":"https://doi.org/10.1530/VB-18-0005","url":null,"abstract":"The year 2018 marked the 110th anniversary of Goldmann’s discovery that vascularization is an active process in tissues1 and the 50th anniversary of the concomitant reports from Greenblatt and Shubik2 and Ehrmann and Knoth3 that soluble morphogenic factors are required for cancer angiogenesis. Many other radically transformative paradigms have been introduced in the last decades. To name a few, the molecular search for the identity of master regulators of vascular tone led to the discovery of the Endothelium-Derived Relaxing Factor (EDRF; i.e., NO4), while clinically inspired investigations led to the recognition of the pathophysiological relevance of neoangiogenesis in cancer and tissue healing. This brought about the proposal of blocking angiogenesis to halt tumor growth and stimulating angiogenesis to treat myocardial ischemia and heart failure5-7.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":"1 1","pages":"E1-E2"},"PeriodicalIF":0.0,"publicationDate":"2019-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38374758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Hytönen, O. Leppänen, J. Taavitsainen, P. Korpisalo, S. Laidinen, K. Alitalo, J. Wadström, T. Rissanen, S. Ylä-Herttuala
Background: Prosthetic vascular grafts in humans characteristically lack confluent endothelialization regardless the duration of implantation. Use of high-porosity grafts has been proposed as a way to induce endothelialization through transgraft capillarization, although early experiments failed to show increased healing in man. Objectives: We hypothesized that transduction of tissues around the prosthetic conduit with vectors encoding VEGF Receptor-2 (VEGFR2) ligands would augment transinterstitial capillarization and induce luminal endothelialization of high-porosity PTFE grafts. Methods: Fifty-two NZW rabbits received 87 ePTFE uni- or bilateral end-to-end interposition grafts in carotid arteries. Rabbits were randomized to local therapy with adenoviruses encoding AdVEGF-A165, AdVEGF-A109 or control AdLacZ and analyzed at 6 and 28d after surgery by contrast-enhanced ultrasound and histology. Results: AdVEGF-A165 and AdVEGF-A109 dramatically increased perfusion in perigraft tissues at 6d (14.2±3.6 or 16.7±2.6- fold increases, P<0.05 and P<0.01). At 28d the effect was no longer significantly higher than baseline. At 6d no luminal endothelialization was observed in any of the groups. At 28d, AdVEGF-A109 and AdVEGF-A165 treated animals showed enhanced ingrowth of transinterstitial capillaries (66.0±13.7% and 77.4±15.7% of graft thickness vs. 44.7±24.4% in controls, P<0.05) and improved luminal endothelialization (11.2±26.3% and 11.4±22.2%, AdVEGF-A109 and AdVEGF-A165 vs. 0% in controls, P<0.05). No increased stenosis was observed in the treatment groups as compared to LacZ controls. Conclusions: This study suggests that transient local overexpression of VEGFR2 ligands in the peri-implant tissues at time of graft implantation is a novel strategy to increase endothelialization of high-porosity ePTFE vascular grafts and improve the patency of small-diameter vascular prostheses.
{"title":"Improved endothelialization of small-diameter ePTFE grafts through growth factor therapy.","authors":"J. Hytönen, O. Leppänen, J. Taavitsainen, P. Korpisalo, S. Laidinen, K. Alitalo, J. Wadström, T. Rissanen, S. Ylä-Herttuala","doi":"10.1530/ec-18-0001","DOIUrl":"https://doi.org/10.1530/ec-18-0001","url":null,"abstract":"Background: Prosthetic vascular grafts in humans characteristically lack confluent endothelialization regardless the duration of implantation. Use of high-porosity grafts has been proposed as a way to induce endothelialization through transgraft capillarization, although early experiments failed to show increased healing in man. \u0000\u0000Objectives: We hypothesized that transduction of tissues around the prosthetic conduit with vectors encoding VEGF Receptor-2 (VEGFR2) ligands would augment transinterstitial capillarization and induce luminal endothelialization of high-porosity PTFE grafts.\u0000\u0000Methods: Fifty-two NZW rabbits received 87 ePTFE uni- or bilateral end-to-end interposition grafts in carotid arteries. Rabbits were randomized to local therapy with adenoviruses encoding AdVEGF-A165, AdVEGF-A109 or control AdLacZ and analyzed at 6 and 28d after surgery by contrast-enhanced ultrasound and histology. \u0000\u0000Results: AdVEGF-A165 and AdVEGF-A109 dramatically increased perfusion in perigraft tissues at 6d (14.2±3.6 or 16.7±2.6- fold increases, P<0.05 and P<0.01). At 28d the effect was no longer significantly higher than baseline. At 6d no luminal endothelialization was observed in any of the groups. At 28d, AdVEGF-A109 and AdVEGF-A165 treated animals showed enhanced ingrowth of transinterstitial capillaries (66.0±13.7% and 77.4±15.7% of graft thickness vs. 44.7±24.4% in controls, P<0.05) and improved luminal endothelialization (11.2±26.3% and 11.4±22.2%, AdVEGF-A109 and AdVEGF-A165 vs. 0% in controls, P<0.05). No increased stenosis was observed in the treatment groups as compared to LacZ controls. \u0000\u0000Conclusions: This study suggests that transient local overexpression of VEGFR2 ligands in the peri-implant tissues at time of graft implantation is a novel strategy to increase endothelialization of high-porosity ePTFE vascular grafts and improve the patency of small-diameter vascular prostheses.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44666263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：