The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
Faisal Sharif - One of the best experts on this subject based on the ideXlab platform.
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gene eluting stents non viral liposome based gene delivery of enos to the Blood Vessel Wall in vivo results in enhanced endothelialization but does not reduce restenosis in a hypercholesterolemic model
Gene Therapy, 2012Co-Authors: Faisal Sharif, Sean O Hynes, J. Crowley, Karl J A Mccullagh, S Ganley, Udo Greiser, P E Mchugh, Frank BarryAbstract:Although successful, drug-eluting stents require significant periods of dual anti-platelet therapy with a persistent risk of late stent thrombosis due to inhibition of re-endothelialization. Endothelial regeneration is desirable to protect against in-stent thrombosis. Gene-eluting stents may be an alternative allowing inhibition of neointima and regenerating endothelium. We have shown that adenoviral endothelial nitric oxide synthase (eNOS) delivery can result in significantly decreased neointimal formation and enhanced re-endothelialization. Here, we examined non-viral reporter and therapeutic gene delivery from a stent. We coated lipoplexes directly onto the surface of stents. These lipostents were then deployed in the injured external iliac artery of either normal or hypercholesterolemic New Zealand White rabbits and recovered after 28 days. Lipoplexes composed of lipofectin and a reporter lacZ gene or therapeutic eNOS gene were used. We demonstrated efficient gene delivery at 28 days post-deployment in the media (21.3±7.5%) and neointima (26.8±11.2%). Liposomal delivery resulted in expression in macrophages between the stent struts. This resulted in improved re-endothelialization as detected by two independent measures compared with vector and stent controls (P<0.05 for both). However, in contrast to viral delivery of eNOS, liposomal eNOS does not reduce restenosis rates. The differing cell populations targeted by lipoplexes compared with adenoviral vectors may explain their ability to enhance re-endothelialization without affecting restenosis. Liposome-mediated gene delivery can result in prolonged and localized transgene expression in the Blood Vessel Wall in vivo. Furthermore, lipoeNOS delivery to the Blood Vessel Wall results in accelerated re-endothelialization; however, it does not reduce neointimal formation.
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gene eluting stents adenovirus mediated delivery of enos to the Blood Vessel Wall accelerates re endothelialization and inhibits restenosis
Molecular Therapy, 2008Co-Authors: Faisal Sharif, Ronan Cooney, Linda Howard, Jill Mcmahon, Sean O Hynes, J. Crowley, K. Daly, Frank Barry, Timothy ObrienAbstract:Drug-eluting stents for coronary artery disease results in inhibition of smooth muscle cell (SMC) and endothelial cells which may increase the risk of stent thrombosis. In this study, we attempted to enhance re-endothelialization of deployed stents while simultaneously inhibiting intimal hyperplasia by overexpression of endothelial nitric oxide synthase (eNOS) delivery in the vasculature using an adenovirus gene–eluting stent. Re-endothelialization was significantly greater in Vessels obtained from normocholesterolemic animals at day 14 (85.34% ± 7.38 versus 62.66% ± 10.49; P P P 2 ± 1.18, AdβGal 0.98 mm 2 ± 0.98, phosphorylcholine (PC) 1.87 mm 2 ± 1.18; P 2 ± 1.13, AdβGal 3.73 mm 2 ± 0.95, PC 3.2 mm 2 ± 0.94; P P P
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gene eluting stents comparison of adenoviral and adeno associated viral gene delivery to the Blood Vessel Wall in vivo
Human Gene Therapy, 2006Co-Authors: Faisal Sharif, Ronan Cooney, Jill Mcmahon, Sean O Hynes, J. Crowley, K. Daly, Siobhan Conroy, Peter Dockery, Garry P Duffy, Jeffrey S BartlettAbstract:Gene-eluting stents are being evaluated in animals as an alternative approach to inhibiting in-stent restenosis. Adeno-associated virus type 2 (AAV2) and adenovirus are commonly used for gene transfer applications. We tested the hypothesis that these vectors can achieve prolonged and localized gene delivery to the Vessel Wall, using stents as delivery platforms. AdβGal (5 × 109 plaque-forming units) and AAV2βGal (5.3 × 109 DNase-resistant particles) were used to coat BiodivYsio stents with matrix HI coating (Abbott Vascular Devices, Galway, Ireland). After balloon injury, external iliac arteries of New Zealand White rabbits were stented. The reverse transcription-polymerase chain reaction was used to assess viral spread. Expression of LacZ was demonstrated with both vectors at five time points (3, 7, 14, 21, and 28 days). In the adenovirus group the median percentage of cells expressing the transgene on day 3 was 2.73%, which increased to a median expression of 7.31% at 28 days (p > 0.05). Expression was ...
Brant E Isakson - One of the best experts on this subject based on the ideXlab platform.
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Hemoglobin α in the Blood Vessel Wall
Free radical biology & medicine, 2014Co-Authors: Joshua T. Butcher, Tyler Johnson, Jody M. Beers, Linda Columbus, Brant E IsaksonAbstract:Hemoglobin has been studied and well characterized in red Blood cells for over 100 years. However, new work has indicated that the hemoglobin α subunit (Hbα) is also found within the Blood Vessel Wall, where it appears to localize at the myoendothelial junction (MEJ) and plays a role in regulating nitric oxide (NO) signaling between endothelium and smooth muscle. This discovery has created a new paradigm for the control of endothelial nitric oxide synthase activity, nitric oxide diffusion, and, ultimately, vascular tone and Blood pressure. This review discusses the current knowledge of hemoglobin׳s properties as a gas exchange molecule in the Bloodstream and extrapolates the properties of Hbα biology to the MEJ signaling domain. Specifically, we propose that Hbα is present at the MEJ to regulate NO release and diffusion in a restricted physical space, which would have powerful implications for the regulation of Blood flow in peripheral resistance arteries.
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Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall
Pharmacological Reviews, 2014Co-Authors: Marie Billaud, Alexander W. Lohman, Lauren A. Biwer, Scott R. Johnstone, Stephanie M. Mutchler, Brant E IsaksonAbstract:It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the Blood Vessel Wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the Blood Vessel Wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to Vessel Wall function.
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Mechanisms of ATP release and signalling in the Blood Vessel Wall
Cardiovascular research, 2012Co-Authors: Alexander W. Lohman, Marie Billaud, Brant E IsaksonAbstract:The nucleotide adenosine 5′-triphosphate (ATP) has classically been considered the cell's primary energy currency. Importantly, a novel role for ATP as an extracellular autocrine and/or paracrine signalling molecule has evolved over the past century and extensive work has been conducted to characterize the ATP-sensitive purinergic receptors expressed on almost all cell types in the body. Extracellular ATP elicits potent effects on vascular cells to regulate Blood Vessel tone but can also be involved in vascular pathologies such as atherosclerosis. While the effects of purinergic signalling in the vasculature have been well documented, the mechanism(s) mediating the regulated release of ATP from cells in the Blood Vessel Wall and circulation are now a key target of investigation. The aim of this review is to examine the current proposed mechanisms of ATP release from vascular cells, with a special emphasis on the transporters and channels involved in ATP release from vascular smooth muscle cells, endothelial cells, circulating red Blood cells, and perivascular sympathetic nerves, including vesicular exocytosis, plasma membrane F1/F0-ATP synthase, ATP-binding cassette (ABC) transporters, connexin hemichannels, and pannexin channels.
Mervin C. Yoder - One of the best experts on this subject based on the ideXlab platform.
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Blood Vessel Wall–Derived Endothelial Colony-Forming Cells Enhance Fracture Repair and Bone Regeneration
Calcified Tissue International, 2011Co-Authors: Kaarthik S. Chandrasekhar, Hongkang Zhou, Pingyu Zeng, Daniel Alge, Brandt A. Finney, Mervin C. YoderAbstract:Endochondral bone formation requires new Blood Vessel formation, and endothelial progenitor cells (EPCs) may play a role in this process. Endothelial colony-forming cells (ECFCs), one subtype of EPCs, isolated from the microvasculature of rat lungs, exhibited cell surface antigen markers and gene products characteristic of endothelial cells and displayed high proliferative potential and an ability to form Vessel-like network structures in vitro. The aim of this study was to evaluate whether ECFCs facilitate bone healing during fracture repair and stimulate bone regeneration. When type I collagen sponge containing ECFCs were surgically wrapped around the fractured femurs of rats, newly formed bone mineral at the site of fracture was 13% greater ( P = 0.01) and energy to failure was 46% greater ( P = 0.01) compared to sponge-wrapped fractures without ECFCs. When ECFCs in type I collagen sponge were surgically implanted into the bone defective area, more new Vessels formed locally in comparison with sponge-alone controls and new bone tissues were seen. Further, co-implantation of ECFCs and hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds at the bone defective sites stimulated more new bone tissues than HA/TCP scaffold alone. These results show that cell therapy with Vessel Wall–derived ECFCs can induce new Vessel formation, stimulate new bone formation, and facilitate bone repair and could be a useful approach to treat non-union fractures and bone defects.
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Blood Vessel Wall derived endothelial colony forming cells enhance fracture repair and bone regeneration
Calcified Tissue International, 2011Co-Authors: Kaarthik S. Chandrasekhar, Hongkang Zhou, Pingyu Zeng, Daniel Alge, Brandt A. Finney, Mervin C. YoderAbstract:Endochondral bone formation requires new Blood Vessel formation, and endothelial progenitor cells (EPCs) may play a role in this process. Endothelial colony- forming cells (ECFCs), one subtype of EPCs, isolated from the microvasculature of rat lungs, exhibited cell surface antigen markers and gene products characteristic of endo- thelial cells and displayed high proliferative potential and an ability to form Vessel-like network structures in vitro. The aim of this study was to evaluate whether ECFCs facilitate bone healing during fracture repair and stimulate bone regeneration. When type I collagen sponge containing ECFCs were surgically wrapped around the fractured femurs of rats, newly formed bone mineral at the site of fracture was 13% greater (P = 0.01) and energy to failure was 46% greater (P = 0.01) compared to sponge-wrapped fractures without ECFCs. When ECFCs in type I collagen sponge were surgically implanted into the bone defective area, more new Vessels formed locally in comparison with sponge-alone controls and new bone tissues were seen. Further, co-implantation of ECFCs and hydroxyapatite/ tricalcium phosphate (HA/TCP) scaffolds at the bone defective sites stimulated more new bone tissues than HA/ TCP scaffold alone. These results show that cell therapy with Vessel Wall-derived ECFCs can induce new Vessel formation, stimulate new bone formation, and facilitate bone repair and could be a useful approach to treat non- union fractures and bone defects.
Sean O Hynes - One of the best experts on this subject based on the ideXlab platform.
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gene eluting stents non viral liposome based gene delivery of enos to the Blood Vessel Wall in vivo results in enhanced endothelialization but does not reduce restenosis in a hypercholesterolemic model
Gene Therapy, 2012Co-Authors: Faisal Sharif, Sean O Hynes, J. Crowley, Karl J A Mccullagh, S Ganley, Udo Greiser, P E Mchugh, Frank BarryAbstract:Although successful, drug-eluting stents require significant periods of dual anti-platelet therapy with a persistent risk of late stent thrombosis due to inhibition of re-endothelialization. Endothelial regeneration is desirable to protect against in-stent thrombosis. Gene-eluting stents may be an alternative allowing inhibition of neointima and regenerating endothelium. We have shown that adenoviral endothelial nitric oxide synthase (eNOS) delivery can result in significantly decreased neointimal formation and enhanced re-endothelialization. Here, we examined non-viral reporter and therapeutic gene delivery from a stent. We coated lipoplexes directly onto the surface of stents. These lipostents were then deployed in the injured external iliac artery of either normal or hypercholesterolemic New Zealand White rabbits and recovered after 28 days. Lipoplexes composed of lipofectin and a reporter lacZ gene or therapeutic eNOS gene were used. We demonstrated efficient gene delivery at 28 days post-deployment in the media (21.3±7.5%) and neointima (26.8±11.2%). Liposomal delivery resulted in expression in macrophages between the stent struts. This resulted in improved re-endothelialization as detected by two independent measures compared with vector and stent controls (P<0.05 for both). However, in contrast to viral delivery of eNOS, liposomal eNOS does not reduce restenosis rates. The differing cell populations targeted by lipoplexes compared with adenoviral vectors may explain their ability to enhance re-endothelialization without affecting restenosis. Liposome-mediated gene delivery can result in prolonged and localized transgene expression in the Blood Vessel Wall in vivo. Furthermore, lipoeNOS delivery to the Blood Vessel Wall results in accelerated re-endothelialization; however, it does not reduce neointimal formation.
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gene eluting stents adenovirus mediated delivery of enos to the Blood Vessel Wall accelerates re endothelialization and inhibits restenosis
Molecular Therapy, 2008Co-Authors: Faisal Sharif, Ronan Cooney, Linda Howard, Jill Mcmahon, Sean O Hynes, J. Crowley, K. Daly, Frank Barry, Timothy ObrienAbstract:Drug-eluting stents for coronary artery disease results in inhibition of smooth muscle cell (SMC) and endothelial cells which may increase the risk of stent thrombosis. In this study, we attempted to enhance re-endothelialization of deployed stents while simultaneously inhibiting intimal hyperplasia by overexpression of endothelial nitric oxide synthase (eNOS) delivery in the vasculature using an adenovirus gene–eluting stent. Re-endothelialization was significantly greater in Vessels obtained from normocholesterolemic animals at day 14 (85.34% ± 7.38 versus 62.66% ± 10.49; P P P 2 ± 1.18, AdβGal 0.98 mm 2 ± 0.98, phosphorylcholine (PC) 1.87 mm 2 ± 1.18; P 2 ± 1.13, AdβGal 3.73 mm 2 ± 0.95, PC 3.2 mm 2 ± 0.94; P P P
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gene eluting stents comparison of adenoviral and adeno associated viral gene delivery to the Blood Vessel Wall in vivo
Human Gene Therapy, 2006Co-Authors: Faisal Sharif, Ronan Cooney, Jill Mcmahon, Sean O Hynes, J. Crowley, K. Daly, Siobhan Conroy, Peter Dockery, Garry P Duffy, Jeffrey S BartlettAbstract:Gene-eluting stents are being evaluated in animals as an alternative approach to inhibiting in-stent restenosis. Adeno-associated virus type 2 (AAV2) and adenovirus are commonly used for gene transfer applications. We tested the hypothesis that these vectors can achieve prolonged and localized gene delivery to the Vessel Wall, using stents as delivery platforms. AdβGal (5 × 109 plaque-forming units) and AAV2βGal (5.3 × 109 DNase-resistant particles) were used to coat BiodivYsio stents with matrix HI coating (Abbott Vascular Devices, Galway, Ireland). After balloon injury, external iliac arteries of New Zealand White rabbits were stented. The reverse transcription-polymerase chain reaction was used to assess viral spread. Expression of LacZ was demonstrated with both vectors at five time points (3, 7, 14, 21, and 28 days). In the adenovirus group the median percentage of cells expressing the transgene on day 3 was 2.73%, which increased to a median expression of 7.31% at 28 days (p > 0.05). Expression was ...
Robert D Rosenberg - One of the best experts on this subject based on the ideXlab platform.
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antisense c myb oligonucleotides inhibit intimal arterial smooth muscle cell accumulation in vivo
Nature, 1992Co-Authors: Michael Simons, Elazer R Edelman, Jeanluc Dekeyser, Robert Langer, Robert D RosenbergAbstract:SYNTHETIC antisense oligonucleotides have been used to dissect gene function in vitro. Technical difficulties prevented the use of this approach for investigating the effect of gene products in vivo. Here we report the use of local delivery of antisense c-myb oligonu-cleotide to suppress intimal accumulation of rat carotid arterial smooth muscle cells. Our results suggest that antisense oligonucleotides can be used to define the in vivo biological role of specific macromolecules in the Blood Vessel Wall and could potentially serve as a new class of therapeutic agents for cardiovascular disorders.