The Experts below are selected from a list of 12174 Experts worldwide ranked by ideXlab platform
J Fisher - One of the best experts on this subject based on the ideXlab platform.
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contrasting biofunctionalization strategies for the enhanced Endothelialization of biodegradable vascular grafts
Biomacromolecules, 2015Co-Authors: Anthony J Melchiorri, Narutoshi Hibino, Tai Yi, Tadahisa Sugiura, Shuhei Tara, Toshiharu Shinoka, Christopher K Breuer, J FisherAbstract:Surface modification of biodegradable vascular grafts is an important strategy to improve the in situ Endothelialization of tissue engineered vascular grafts (TEVGs) and prevent major complications associated with current synthetic grafts. Important strategies for improving Endothelialization include increasing endothelial cell mobilization and increased endothelial cell capture through biofunctionalization of TEVGs. The objective of this study was to assess two biofunctionalization strategies for improving Endothelialization of biodegradable polyester vascular grafts. These techniques consisted of cross-linking heparin to graft surfaces to immobilize vascular endothelial growth factor (VEGF) or antibodies against CD34 (anti-CD34Ab). To this end, heparin, VEGF, and anti-CD34Ab attachment and quantification assays confirmed the efficacy of the modification strategy. Cell attachment and proliferation on these groups were compared to unmodified grafts in vitro and in vivo. To assess in vivo graft functionali...
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strategies and techniques to enhance the in situ Endothelialization of small diameter biodegradable polymeric vascular grafts
Tissue Engineering Part B-reviews, 2013Co-Authors: Anthony J Melchiorri, Narutoshi Hibino, J FisherAbstract:Due to the lack of success in small-diameter (<6 mm) prosthetic vascular grafts, a variety of strategies have evolved utilizing a tissue-engineering approach. Much of this work has focused on enhancing the Endothelialization of these grafts. A healthy, confluent endothelial layer provides dynamic control over homeo-stasis, influencing and preventing thrombosis and smooth muscle cell proliferation that can lead to intimal hyperplasia. Strategies to improve Endothelialization of biodegradable polymeric grafts have encompassed both chemical and physical modifications to graft surfaces, many focusing on the recruitment of endothelial and endothelial progenitor cells. This review aims to provide a compilation of current and developing strategies that utilize in situ Endothelialization to improve vascular graft outcomes, providing a context for the future directions of vascular tissue-engineering strategies that do not require preprocedural cell seeding.
Felix C. Tanner - One of the best experts on this subject based on the ideXlab platform.
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pi3k p110α inhibition selectively interferes with arterial thrombosis and neointima formation but not re Endothelialization potential implications for drug eluting stent design
European Heart Journal, 2014Co-Authors: Erik W. Holy, Philipp Jakob, Thomas Eickner, Giovanni G. Camici, Jürg H. Beer, Thomas F. Lüscher, Alexander Akhmedov, Klaus-peter Schmitz, Katrin Sternberg, Felix C. TannerAbstract:Background Impaired re-Endothelialization and stent thrombosis are a safety concern associated with drug-eluting stents (DES). PI3K/p110α controls cellular wound healing pathways, thereby representing an emerging drug target to modulate vascular homoeostasis after injury. Methods and results PI3K/p110α was inhibited by treatment with the small molecule inhibitor PIK75 or a specific siRNA. Arterial thrombosis, neointima formation, and re-Endothelialization were studied in a murine carotid artery injury model. Proliferation and migration of human vascular smooth muscle cell (VSMC) and endothelial cell (EC) were assessed by cell number and Boyden chamber, respectively. Endothelial senescence was evaluated by the β-galactosidase assay, endothelial dysfunction by organ chambers for isometric tension. Arterial thrombus formation was delayed in mice treated with PIK75 when compared with controls. PIK75 impaired arterial expression and activity of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1); in contrast, plasma clotting and platelet aggregation did not differ. In VSMC and EC, PIK75 inhibited expression and activity of TF and PAI-1. These effects occurred at the transcriptional level via the RhoA signalling cascade and the transcription factor NFkB. Furthermore, inhibition of PI3K/p110α with PIK75 or a specific siRNA selectively impaired proliferation and migration of VSMC while sparing EC completely. Treatment with PIK75 did not induce endothelial senescence nor inhibit endothelium-dependent relaxations. In line with this observation, treatment with PIK75 selectively inhibited neointima formation without affecting re-Endothelialization following vascular injury. Conclusion Following vascular injury, PI3K/p110α inhibition selectively interferes with arterial thrombosis and neointima formation, but not re-Endothelialization. Hence, PI3K/p110α represents an attractive new target in DES design.
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PI3K/p110α inhibition selectively interferes with arterial thrombosis and neointima formation, but not re-Endothelialization: Potential implications for drug-eluting stent design
European Heart Journal, 2014Co-Authors: Erik W. Holy, Philipp Jakob, Thomas Eickner, Giovanni G. Camici, Jürg H. Beer, Thomas F. Lüscher, Alexander Akhmedov, Klaus-peter Schmitz, Katrin Sternberg, Felix C. TannerAbstract:Background Impaired re-Endothelialization and stent thrombosis are a\nsafety concern associated with drug-eluting stents ( DES). PI3K/p110\nalpha controls cellular wound healing pathways, thereby representing an\nemerging drug target to modulate vascular homoeostasis after injury.\nMethods and results PI3K/p110 alpha was inhibited by treatment with the\nsmall molecule inhibitor PIK75 or a specific siRNA. Arterial thrombosis,\nneointima formation, and re-Endothelialization were studied in a murine\ncarotid artery injury model. Proliferation and migration of human\nvascular smooth muscle cell (VSMC) and endothelial cell (EC) were\nassessed by cell number and Boyden chamber, respectively. Endothelial\nsenescence was evaluated by the beta-galactosidase assay, endothelial\ndysfunction by organ chambers for isometric tension. Arterial thrombus\nformation was delayed in mice treated with PIK75 when compared with\ncontrols. PIK75 impaired arterial expression and activity of tissue\nfactor (TF) and plasminogen activator inhibitor-1 (PAI-1); in contrast,\nplasma clotting and platelet aggregation did not differ. In VSMC and EC,\nPIK75 inhibited expression and activity of TF and PAI-1. These effects\noccurred at the transcriptional level via the RhoA signalling cascade\nand the transcription factor NFkB. Furthermore, inhibition of PI3K/p110\nalpha with PIK75 or a specific siRNA selectively impaired proliferation\nand migration of VSMC while sparing EC completely. Treatment with PIK75\ndid not induce endothelial senescence nor inhibit endothelium-dependent\nrelaxations. In line with this observation, treatment with PIK75\nselectively inhibited neointima formation without affecting\nre-Endothelialization following vascular injury.\nConclusion Following vascular injury, PI3K/p110 alpha inhibition\nselectively interferes with arterial thrombosis and neointima formation,\nbut not re-Endothelialization. Hence, PI3K/p110 alpha represents an\nattractive new target in DES design.
Anthony J Melchiorri - One of the best experts on this subject based on the ideXlab platform.
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contrasting biofunctionalization strategies for the enhanced Endothelialization of biodegradable vascular grafts
Biomacromolecules, 2015Co-Authors: Anthony J Melchiorri, Narutoshi Hibino, Tai Yi, Tadahisa Sugiura, Shuhei Tara, Toshiharu Shinoka, Christopher K Breuer, J FisherAbstract:Surface modification of biodegradable vascular grafts is an important strategy to improve the in situ Endothelialization of tissue engineered vascular grafts (TEVGs) and prevent major complications associated with current synthetic grafts. Important strategies for improving Endothelialization include increasing endothelial cell mobilization and increased endothelial cell capture through biofunctionalization of TEVGs. The objective of this study was to assess two biofunctionalization strategies for improving Endothelialization of biodegradable polyester vascular grafts. These techniques consisted of cross-linking heparin to graft surfaces to immobilize vascular endothelial growth factor (VEGF) or antibodies against CD34 (anti-CD34Ab). To this end, heparin, VEGF, and anti-CD34Ab attachment and quantification assays confirmed the efficacy of the modification strategy. Cell attachment and proliferation on these groups were compared to unmodified grafts in vitro and in vivo. To assess in vivo graft functionali...
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strategies and techniques to enhance the in situ Endothelialization of small diameter biodegradable polymeric vascular grafts
Tissue Engineering Part B-reviews, 2013Co-Authors: Anthony J Melchiorri, Narutoshi Hibino, J FisherAbstract:Due to the lack of success in small-diameter (<6 mm) prosthetic vascular grafts, a variety of strategies have evolved utilizing a tissue-engineering approach. Much of this work has focused on enhancing the Endothelialization of these grafts. A healthy, confluent endothelial layer provides dynamic control over homeo-stasis, influencing and preventing thrombosis and smooth muscle cell proliferation that can lead to intimal hyperplasia. Strategies to improve Endothelialization of biodegradable polymeric grafts have encompassed both chemical and physical modifications to graft surfaces, many focusing on the recruitment of endothelial and endothelial progenitor cells. This review aims to provide a compilation of current and developing strategies that utilize in situ Endothelialization to improve vascular graft outcomes, providing a context for the future directions of vascular tissue-engineering strategies that do not require preprocedural cell seeding.
Masataka Sata - One of the best experts on this subject based on the ideXlab platform.
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fluvastatin accelerates re Endothelialization impaired by local sirolimus treatment
European Journal of Pharmacology, 2009Co-Authors: Daiju Fukuda, Soichiro Enomoto, Ibuki Shirakawa, Ryozo Nagai, Masataka SataAbstract:Abstract Sirolimus-eluting stent reduces restenosis after percutaneous coronary intervention. However, accumulating evidence suggests that sirolimus potentially affects re-Endothelialization, leading to late thrombosis. Statins have protective effects on endothelium. Recently, statins are reported to increase the number of circulating endothelial progenitor cells (EPCs) and accelerate re-Endothelialization after vascular injury. Here, we tested the hypothesis that fluvastatin has beneficial effect on re-Endothelialization after local sirolimus treatment. We performed wire-mediated vascular injury to both sides of femoral arteries of wild-type mice and bone marrow chimeric mice. Either sirolimus (100 μg) or DMSO was administered locally to the perivascular area of the injured arteries. All mice received either fluvastatin (5 mg/kg/day) or vehicle by gavage starting at one week before the surgery until sacrifice. At 4 weeks after the surgery, re-Endothelialization of the sirolimus-treated artery was significantly less than that of DMSO-treated one in the vehicle-treated mice as determined by the percentage of CD31-positive area ( P P = NS). Contribution of bone marrow-derived cells to re-Endothelialization was seldom observed in bone marrow chimeric mice regardless of fluvastatin administration. Fluvastatin significantly ameliorated proliferation (2.5-folds) and migration activities (2.3-folds) of mature endothelial cells impaired by sirolimus treatment ( P P
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Fluvastatin accelerates re-Endothelialization impaired by local sirolimus treatment.
European journal of pharmacology, 2009Co-Authors: Daiju Fukuda, Soichiro Enomoto, Ibuki Shirakawa, Ryozo Nagai, Masataka SataAbstract:Sirolimus-eluting stent reduces restenosis after percutaneous coronary intervention. However, accumulating evidence suggests that sirolimus potentially affects re-Endothelialization, leading to late thrombosis. Statins have protective effects on endothelium. Recently, statins are reported to increase the number of circulating endothelial progenitor cells (EPCs) and accelerate re-Endothelialization after vascular injury. Here, we tested the hypothesis that fluvastatin has beneficial effect on re-Endothelialization after local sirolimus treatment. We performed wire-mediated vascular injury to both sides of femoral arteries of wild-type mice and bone marrow chimeric mice. Either sirolimus (100 microg) or DMSO was administered locally to the perivascular area of the injured arteries. All mice received either fluvastatin (5 mg/kg/day) or vehicle by gavage starting at one week before the surgery until sacrifice. At 4 weeks after the surgery, re-Endothelialization of the sirolimus-treated artery was significantly less than that of DMSO-treated one in the vehicle-treated mice as determined by the percentage of CD31-positive area (P
Erik W. Holy - One of the best experts on this subject based on the ideXlab platform.
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pi3k p110α inhibition selectively interferes with arterial thrombosis and neointima formation but not re Endothelialization potential implications for drug eluting stent design
European Heart Journal, 2014Co-Authors: Erik W. Holy, Philipp Jakob, Thomas Eickner, Giovanni G. Camici, Jürg H. Beer, Thomas F. Lüscher, Alexander Akhmedov, Klaus-peter Schmitz, Katrin Sternberg, Felix C. TannerAbstract:Background Impaired re-Endothelialization and stent thrombosis are a safety concern associated with drug-eluting stents (DES). PI3K/p110α controls cellular wound healing pathways, thereby representing an emerging drug target to modulate vascular homoeostasis after injury. Methods and results PI3K/p110α was inhibited by treatment with the small molecule inhibitor PIK75 or a specific siRNA. Arterial thrombosis, neointima formation, and re-Endothelialization were studied in a murine carotid artery injury model. Proliferation and migration of human vascular smooth muscle cell (VSMC) and endothelial cell (EC) were assessed by cell number and Boyden chamber, respectively. Endothelial senescence was evaluated by the β-galactosidase assay, endothelial dysfunction by organ chambers for isometric tension. Arterial thrombus formation was delayed in mice treated with PIK75 when compared with controls. PIK75 impaired arterial expression and activity of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1); in contrast, plasma clotting and platelet aggregation did not differ. In VSMC and EC, PIK75 inhibited expression and activity of TF and PAI-1. These effects occurred at the transcriptional level via the RhoA signalling cascade and the transcription factor NFkB. Furthermore, inhibition of PI3K/p110α with PIK75 or a specific siRNA selectively impaired proliferation and migration of VSMC while sparing EC completely. Treatment with PIK75 did not induce endothelial senescence nor inhibit endothelium-dependent relaxations. In line with this observation, treatment with PIK75 selectively inhibited neointima formation without affecting re-Endothelialization following vascular injury. Conclusion Following vascular injury, PI3K/p110α inhibition selectively interferes with arterial thrombosis and neointima formation, but not re-Endothelialization. Hence, PI3K/p110α represents an attractive new target in DES design.
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PI3K/p110α inhibition selectively interferes with arterial thrombosis and neointima formation, but not re-Endothelialization: Potential implications for drug-eluting stent design
European Heart Journal, 2014Co-Authors: Erik W. Holy, Philipp Jakob, Thomas Eickner, Giovanni G. Camici, Jürg H. Beer, Thomas F. Lüscher, Alexander Akhmedov, Klaus-peter Schmitz, Katrin Sternberg, Felix C. TannerAbstract:Background Impaired re-Endothelialization and stent thrombosis are a\nsafety concern associated with drug-eluting stents ( DES). PI3K/p110\nalpha controls cellular wound healing pathways, thereby representing an\nemerging drug target to modulate vascular homoeostasis after injury.\nMethods and results PI3K/p110 alpha was inhibited by treatment with the\nsmall molecule inhibitor PIK75 or a specific siRNA. Arterial thrombosis,\nneointima formation, and re-Endothelialization were studied in a murine\ncarotid artery injury model. Proliferation and migration of human\nvascular smooth muscle cell (VSMC) and endothelial cell (EC) were\nassessed by cell number and Boyden chamber, respectively. Endothelial\nsenescence was evaluated by the beta-galactosidase assay, endothelial\ndysfunction by organ chambers for isometric tension. Arterial thrombus\nformation was delayed in mice treated with PIK75 when compared with\ncontrols. PIK75 impaired arterial expression and activity of tissue\nfactor (TF) and plasminogen activator inhibitor-1 (PAI-1); in contrast,\nplasma clotting and platelet aggregation did not differ. In VSMC and EC,\nPIK75 inhibited expression and activity of TF and PAI-1. These effects\noccurred at the transcriptional level via the RhoA signalling cascade\nand the transcription factor NFkB. Furthermore, inhibition of PI3K/p110\nalpha with PIK75 or a specific siRNA selectively impaired proliferation\nand migration of VSMC while sparing EC completely. Treatment with PIK75\ndid not induce endothelial senescence nor inhibit endothelium-dependent\nrelaxations. In line with this observation, treatment with PIK75\nselectively inhibited neointima formation without affecting\nre-Endothelialization following vascular injury.\nConclusion Following vascular injury, PI3K/p110 alpha inhibition\nselectively interferes with arterial thrombosis and neointima formation,\nbut not re-Endothelialization. Hence, PI3K/p110 alpha represents an\nattractive new target in DES design.