Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft Mitsuteru Handa, MD, Wei Li,

Slides:

Advertisements

Similar presentations

The Role of ex-vivo Gene Therapy of Vein Grafts with Egr-1 Decoy in the Suppression of Intimal Hyperplasia M. Peroulis, J. Kakisis, A. Kapelouzou, A.

Advertisements

Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half.

Vascular endothelial growth factor-C derived from CD11b+ cells induces therapeutic improvements in a murine model of hind limb ischemia Go Kuwahara,

Dipeptidyl peptidase 4 inhibitor reduces intimal hyperplasia in rabbit autologous jugular vein graft under poor distal runoff Akio Koyama, MD, Kimihiro.

Inhibition of smooth muscle cell migration and neointima formation in vein grafts by overexpression of matrix metalloproteinase-3 Klaus Kallenbach, MD,

Mesenchymal stem cells attenuate angiotensin II-induced aortic aneurysm growth in apolipoprotein E-deficient mice Ryotaro Hashizume, MD, Aika Yamawaki-Ogata,

Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half.

Reduced hind limb ischemia-reperfusion injury in Toll-like receptor-4 mutant mice is associated with decreased neutrophil extracellular traps Rahmi Oklu,

Elastic fibers reconstructed using adenovirus-mediated expression of tropoelastin and tested in the elastase model of abdominal aortic aneurysm in rats

Zinc finger protein 191 deficiency attenuates vascular smooth muscle cell proliferation, migration, and intimal hyperplasia after endovascular arterial.

The therapeutic effect of vascular endothelial growth factor gene- or heme oxygenase-1 gene-modified endothelial progenitor cells on neovascularization.

Endogenous superoxide dismutase activation by oral administration of riboflavin reduces abdominal aortic aneurysm formation in rats Zhenhai Yu, MD, Keisuke.

Xue Ma, MD, Jeffrey D. Pearce, MD, David B. Wilson, MD, William P

An engineered vascular endothelial growth factor-activating transcription factor induces therapeutic angiogenesis in ApoE knockout mice with hindlimb.

Celiprolol reduces the intimal thickening of autogenous vein grafts via an enhancement of nitric oxide function through an inhibition of superoxide production

Low molecular weight (LMW) heparin inhibits injury-induced femoral artery remodeling in mouse via upregulating CD44 expression Gaofeng Zhao, MD, PhD,

Ezetimibe reduces intimal hyperplasia in rabbit jugular vein graft

Inhibitory effects of mesenchymal stem cells in intimal hyperplasia after balloon angioplasty Ae-Kyeong Kim, PhD, Min-Hee Kim, Do-Hyung Kim, Ha-Nl Go,

Pressure distention compared with pharmacologic relaxation in vein grafting upregulates matrix metalloproteinase-2 and -9 Ada W.Y. Chung, PhD, Pooja.

Loss of STAT1 is associated with increased aortic rupture in an experimental model of aortic dissection and aneurysm formation Matthew J. Eagleton, MD,

Gene transduction into aortic wall using plasmid-loaded cationized gelatin hydrogel- coated polyester stent graft Hongshan Zhong, MD, Osamu Matsui, MD,

Inhibitory Effects of Calcitonin Gene-Related Peptides on Experimental Vein Graft Disease Xiaoning Zhang, MD, Jian Zhuang, MD, Hongsui Wu, MB, Zhihong.

The cyclolignan picropodophyllin attenuates intimal hyperplasia after rat carotid balloon injury by blocking insulin-like growth factor-1 receptor signaling

Gene transduction into aortic wall using plasmid-loaded cationized gelatin hydrogel- coated polyester stent graft Hongshan Zhong, MD, Osamu Matsui, MD,

Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis

Dipeptidyl peptidase 4 inhibitor reduces intimal hyperplasia in rabbit autologous jugular vein graft under poor distal runoff Akio Koyama, MD, Kimihiro.

Blood-derived smooth muscle cells as a target for gene delivery

Association of smooth muscle cell phenotypes with extracellular matrix disorders in thoracic aortic dissection Lixin Wang, MD, PhD, Jing Zhang, MD, PhD,

Combination of stromal-derived factor-1α and vascular endothelial growth factor gene- modified endothelial progenitor cells is more effective for ischemic.

Transforming growth factor-β increases vascular smooth muscle cell proliferation through the Smad3 and extracellular signal-regulated kinase mitogen-activated.

Use of Brilliant Blue FCF during vein graft preparation inhibits intimal hyperplasia Michael J. Osgood, MD, Kevin Sexton, MD, Igor Voskresensky, MD, Kyle.

Hemagglutinating virus of Japan-liposome–mediated gene transfer of endothelial cell nitric oxide synthase inhibits intimal hyperplasia of canine vein.

Karen M. Newman, PhD, Jessie Jean-Claude, MD, Hong Li, MS, John V

Adenovirus-mediated intra-arterial delivery of cellular repressor of E1A-stimulated genes inhibits neointima formation in rabbits after balloon injury

Increased connexin43 expression in human saphenous veins in culture is associated with intimal hyperplasia Sébastien Déglise, MD, David Martin, MS, Hervé.

Orally administered dipeptidyl peptidase-4 inhibitor (alogliptin) prevents abdominal aortic aneurysm formation through an antioxidant effect in rats

Free-radical scavenger edaravone inhibits both formation and development of abdominal aortic aneurysm in rats Keisuke Morimoto, MD, Tomomi Hasegawa,

Differential expression of elastin assembly genes in patients with Stanford Type A aortic dissection using microarray analysis Bernice L.Y. Cheuk, PhD,

Mikko I. Mäyränpää, MD, PhD, Julia A

Thomas E. Arnold, MD, Dmitri Gnatenko, PhD, Wadie F. Bahou, MD

Daniel J. Wong, MD, Daniel Y. Lu, MD, Clinton D

Effect of microRNA-145 to prevent vein graft disease in rabbits by regulation of smooth muscle cell phenotype Motoaki Ohnaka, MD, Akira Marui, MD, PhD,

Magnetic nanosphere-guided site-specific delivery of vascular endothelial growth factor gene attenuates restenosis in rabbit balloon-injured artery Tiemin.

Antisense to transforming growth factor-β1 messenger RNA reduces vein graft intimal hyperplasia and monocyte chemotactic protein 1 Randal A. Wolff, PhD,

Sarpogrelate hydrochloride reduced intimal hyperplasia in experimental rabbit vein graft Akio Kodama, MD, Kimihiro Komori, MD, PhD, Keisuke Hattori, MD,

Spatiotemporal expression and localization of matrix metalloproteinas-9 in a murine model of thoracic aortic aneurysm Jeffrey A. Jones, PhD, John R.

Leptin receptor is elevated in carotid plaques from neurologically symptomatic patients and positively correlated with augmented macrophage density Jacob.

Recanalization of arterial thrombus, and inhibition with β-radiation in a new murine carotid occlusion model: mRNA expression of angiopoietins, metalloproteinases,

In vivo suppression of vein graft disease by nonviral, electroporation-mediated, gene transfer of tissue inhibitor of metalloproteinase-1 linked to the.

Adventitial endothelial implants reduce matrix metalloproteinase-2 expression and increase luminal diameter in porcine arteriovenous grafts Helen M.

Harry M. Salinas, MD, Saiqa I. Khan, MD, Michael C

Survivin expression is up-regulated in vascular injury and identifies a distinct cellular phenotype Hector F. Simosa, MD, Grace Wang, MD, XinXin Sui,

Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft Mitsuteru Handa, MD, Wei Li,

Gene delivery to in situ veins: Differential effects of adenovirus and adeno-associated viral vectors Mohammad H. Eslami, MD, Sidhu P. Gangadharan, MD,

Navin K. Kapur, MD, Ce Bian, MD, Edward Lin, MD, Clayton B

Adventitial versus intimal liposome-mediated ex vivo transfection of canine saphenous vein grafts with endothelial nitric oxide synthase gene Manju Kalra,

Hepatocyte growth factor prevents intimal hyperplasia in rabbit carotid expanded polytetrafluoroethylene grafting Masakazu Harada, MD, Hiroaki Takenaka,

Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques Benjamin J. Dunmore, PhD, Mark J. McCarthy,

In vitro differences between smooth muscle cells derived from varicose veins and normal veins Ying Xiao, PhD, Zhibin Huang, MD, Henghui Yin, PhD, Ying.

Association of smooth muscle cell phenotypic modulation with extracellular matrix alterations during neointima formation in rabbit vein grafts Wei-da.

Cathepsin G deficiency reduces periaortic calcium chloride injury-induced abdominal aortic aneurysms in mice Jing Wang, MD, PhD, Galina K. Sukhova, PhD,

Neointimal hyperplasia on a cell-seeded polytetrafluoroethylene graft is promoted by transfer of tissue plasminogen activator gene and inhibited by transfer.

Inhibition of N-cadherin retards smooth muscle cell migration and intimal thickening via induction of apoptosis Cressida A. Lyon, PhD, Evgenia Koutsouki,

Temporal genomics of vein bypass grafting through oligonucleotide microarray analysis Jeffrey A Kalish, MD, David J Willis, MD, Cheng Li, PhD, Jeffrey.

Vein interposition cuffs decrease the intimal hyperplastic response of polytetrafluoroethylene bypass grafts Mark Kissin, MD, Nikhil Kansal, MD, Peter.

Blockade of monocyte chemoattractant protein-1 by adenoviral gene transfer inhibits experimental vein graft neointimal formation Hideki Tatewaki, MD,

Macrophage depletion reduces monocyte chemotactic protein-1 and transforming growth factor-β1 in healing rat vein grafts Randal A Wolff, PhD, Jeffrey.

Dustin M. Bermudez, MD, Junwang Xu, MD, Benjamin J

Controlled release of small interfering RNA targeting midkine attenuates intimal hyperplasia in vein grafts Hiroshi Banno, MD, Yoshifumi Takei, PhD,

Differential transcriptional activation of matrix metalloproteinase-2 and membrane type-1 matrix metalloproteinase by experimental deep venous thrombosis.

Presentation transcript:

Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft Mitsuteru Handa, MD, Wei Li, MD, PhD, Kouichi Morioka, MD, PhD, Atsushi Takamori, MD, Narihisa Yamada, MD, PhD, Akio Ihaya, MD, PhD Journal of Vascular Surgery Volume 48, Issue 6, Pages 1566-1574 (December 2008) DOI: 10.1016/j.jvs.2008.07.029 Copyright © 2008 The Society for Vascular Surgery Terms and Conditions

Fig 1 Determination of optimal gene transfer efficiency. A and B, Representative gross views are shown of X-gal staining of whole vein grafts. C and D, Photomicrographs of sections of vein grafts 7 days are shown after implantation and gene transfection (scale bars, 100 μm). Panels A and C were from grafts treated with poloxamer hydrogel containing LacZ alone; and B and D were from grafts treated with poloxamer hydrogel containing 0.25% trypsin and LacZ. E, The percentage of cells stained positive for LacZ is shown in the adventitia (A, black bars) and intima and media (IM, gray bars).*P < .01 vs 0% trypsin, and †P < .01 vs 0.1% trypsin. F, Intima thickness after 1 week of graft implantation is shown for different concentrations of trypsin. Error bars indicate the standard deviation. Journal of Vascular Surgery 2008 48, 1566-1574DOI: (10.1016/j.jvs.2008.07.029) Copyright © 2008 The Society for Vascular Surgery Terms and Conditions

Fig 2 Effects of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) on the development of intimal hyperplasia of vein grafts at 2 (2W) and 8 weeks (8W) after implantation and gene transfection. A, Representative images show the middle portion of vein graphs from rabbits that received saline, 20% poloxamer F127 hydrogel containing 0.25% trypsin and plasmid encoding human PD-ECGF/TP (pCIhTP group), and rabbits receiving the hydrogel containing the LacZ gene (pCILacZ group). Elastica van Gieson staining; the scale bar equals 200 μm, and the dashed line indicates the border of intima (I) and media. Quantitative analysis of the (B) intimal thickness and (C) intimal areas of vein grafts in saline (dark gray bars), pCILacZ (light gray bars), and pCIhTP (white bars) groups indicated they were decreased in treated group. Error bars show the standard deviation; *P < .01, pCIhTP vs pCILacZ and saline. Journal of Vascular Surgery 2008 48, 1566-1574DOI: (10.1016/j.jvs.2008.07.029) Copyright © 2008 The Society for Vascular Surgery Terms and Conditions

Fig 3 Assessment of heme oxygenase-1 expression and vascular smooth muscle cell (VSMC) proliferation index in the vein grafts. A, Immunohistochemical staining for heme oxygenase-1 (brown) and (B) representative images of double immunohistochemical staining for proliferative cell nuclear antigen (PCNA; brown) and VSMCs (pink) at 2 weeks are shown. The arrowheads indicate the double positively stained VSMCs, and the dashed line indicates the border of the intima (I) and media. Scale bar equals 100 μm. C, Quantitative analysis of the ratio of PCNA-positive cells in the intimal areas of vein graphs at 2 and 8 weeks from rabbits that received saline, 20% poloxamer F127 hydrogel containing 0.25% trypsin and plasmid encoding human platelet-derived endothelial cell growth factor/thymidine phosphorylase (pCIhTP group), and rabbits receiving the hydrogel containing the LacZ gene (pCILacZ group). Error bars show the standard deviation; *P < .01, pCIhTP vs pCILacZ and saline. Journal of Vascular Surgery 2008 48, 1566-1574DOI: (10.1016/j.jvs.2008.07.029) Copyright © 2008 The Society for Vascular Surgery Terms and Conditions

Fig 4 Identification of transgene expression. Total RNA was extracted from vein graft or spleen and reverse transcriptase-polymerase chain reaction (RT-PCR) assay was performed for (A) human platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) in grafts at 2 and 8 weeks, or (B) the LacZ gene in grafts and spleen at 1, 2, and 8 weeks. RT-PCR assay for rabbit β-actin was examined as an RNA quality and loading control. C, Immunoblotting analysis of human PD-ECGF/TP protein 2 weeks after graft implantation. Actin was reblotted as a loading control in the same membrane. D and E, Immunohistochemical staining for human PD-ECGF/TP in the rabbits that received 20% poloxamer F127 hydrogel containing 0.25% trypsin and PD-ECGF (pCIhTP) group at (D) 2 weeks and (E) 8 weeks after operation (200× magnification). Cells stained positive for PD-ECGF/TP are brown, and arrowheads indicate representative staining. Journal of Vascular Surgery 2008 48, 1566-1574DOI: (10.1016/j.jvs.2008.07.029) Copyright © 2008 The Society for Vascular Surgery Terms and Conditions

Fig 5 Scheme of effect of platelet-derived endothelial cell growth factor/thymidine phosphorylase on vascular smooth muscle cells (VSMC) and the endothelium. The red arrows indicate promotive effect, and blue lines (⊥) indicates an inhibitory effect. 2-DDR-1, 2-deoxy-d-ribose 1-phosphate; HO-1, heme oxygenase-1; IL, interleukin; MMP, matrix metalloproteinase; TP, thymidine phosphorylase; VEGF, vascular endothelial growth factor, Cyto-c, Cytochrome C; Bcl-2 (anti-apoptosis) and Bax (pro-apoptosis), members of Bcl-2 gene family; VSMC, vascular smooth muscle cell. Journal of Vascular Surgery 2008 48, 1566-1574DOI: (10.1016/j.jvs.2008.07.029) Copyright © 2008 The Society for Vascular Surgery Terms and Conditions