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

Slides:

Advertisements

Similar presentations

Development and regression of intimal thickening of arterially transplanted autologous vein grafts in dogs Kazumasa Morinaga, M.D., Hiroshi Eguchi, M.D.,

Advertisements

Assessment of mouse hind limb endothelial function by measuring femoral artery blood flow responses Chao-Hung Wang, MD, Kuo-Ti Chen, MS, Hsiu-Fu Mei,

Diet-induced obesity drives negative mouse vein graft wall remodeling

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

Inflammatory responses involving tumor necrosis factor receptor-associated factor 6 contribute to in-stent lesion formation in a stent implantation model.

Kenneth M. DeSart, MD, Khayree Butler, MD, Kerri A

Effect of tissue plasminogen activator on vascular smooth muscle cells

Perivascular innate immune events modulate early murine vein graft adaptations Binh T. Nguyen, MD, Peng Yu, MD, Ming Tao, MD, Shuai Hao, BS, Tianyu Jiang,

Coarctation-induced degenerative abdominal aortic aneurysm in a porcine model Pao-Yen Lin, MD, Yeng-Ting Wu, MS, Guan-Cheng Lin, BS, Yao Hsiang Shih,

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

Ezetimibe reduces intimal hyperplasia in rabbit jugular vein graft

Alexey V. Kamenskiy, PhD, Iraklis I. Pipinos, MD, PhD, Jeffrey S

Chun-Yu Wong, MD, Margreet R. de Vries, BSc, Yang Wang, MD, Joost R

Transglutaminase type 2 in human abdominal aortic aneurysm is a potential factor in the stabilization of extracellular matrix Sung Shin, MD, Yong-Pil.

Chronic treatment of hydroxytryptamine type 2a receptor antagonist sarpogrelate hydrochloride modulates the vasoreactivity of serotonin in experimental.

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

Effect of blocking platelet activation with AZD6140 on development of abdominal aortic aneurysm in a rat aneurysmal model Jianping Dai, MD, PhD, Liliane.

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

Histologic analysis of stent graft oversizing in the thoracic aorta

Matrix metalloproteinase inhibition reduces intimal hyperplasia in a porcine arteriovenous-graft model Joris I Rotmans, MD, Evelyn Velema, BSc, Hence.

Modification of the descending thoracic aortic anastomotic site using biodegradable felt: Study in a canine model with or without basic fibroblast growth.

Controlled release of ascorbic acid from gelatin hydrogel attenuates abdominal aortic aneurysm formation in rat experimental abdominal aortic aneurysm.

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.

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

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

Vida K. Stark, MS, Thomas F. Warner, MD, John R. Hoch, MD

Brilliant blue FCF is a nontoxic dye for saphenous vein graft marking that abrogates response to injury Kyle M. Hocking, PhD, Weifeng Luo, PhD, Fan Dong.

Diet-induced obesity drives negative mouse vein graft wall remodeling

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,

Alterations in wall tension and shear stress modulate tyrosine kinase signaling and wall remodeling in experimental vein grafts Tam T.T. Huynh, MD, Mark.

Endothelium-dependent vasorelaxations in response to aggregating platelets are impaired in reversed vein grafts Kimihiro Komori, MD, Peter Gloviczki,

Paclitaxel coating of the luminal surface of hemodialysis grafts with effective suppression of neointimal hyperplasia Insu Baek, MS, Cheng Zhe Bai, PhD,

Midkine is expressed by infiltrating macrophages in in-stent restenosis in hypercholesterolemic rabbits Hiroshi Narita, MD, Sen Chen, PhD, Kimihiro Komori,

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

Impaired graft healing due to hypercholesterolemia is prevented by dietary supplementation with α-tocopherol Keiko Miyazaki, MD, Scott M. Colles, PhD,

Coarctation-induced degenerative abdominal aortic aneurysm in a porcine model Pao-Yen Lin, MD, Yeng-Ting Wu, MS, Guan-Cheng Lin, BS, Yao Hsiang Shih,

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

Role of hemodynamic forces in the ex vivo arterialization of human saphenous veins Xavier Berard, MD, PhD, Sébastien Déglise, MD, Florian Alonso, PhD,

Assessment of mouse hind limb endothelial function by measuring femoral artery blood flow responses Chao-Hung Wang, MD, Kuo-Ti Chen, MS, Hsiu-Fu Mei,

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

Annette Ebner, PhD, David M. Poitz, PhD, Antje Augstein, PhD, Ruth H

Matrix metalloproteinase inhibition reduces intimal hyperplasia in a porcine arteriovenous-graft model Joris I Rotmans, MD, Evelyn Velema, BSc, Hence.

Prolonged increases in vein wall tension increase matrix metalloproteinases and decrease constriction in rat vena cava: Potential implications in varicose.

Effects of thrombolysis and venous thrombectomy on valvular competence, thrombogenicity, venous wall morphology, and function Jae-Sung Cho, MD, Eugenio.

The effects of ginsenoside Rb1 on endothelial damage and ghrelin expression induced by hyperhomocysteine Zhiwei Xu, PhD, Taohua Lan, MD, Weikang Wu,

Perivascular delivery of losartan with surgical fibrin glue prevents neointimal hyperplasia after arterial injury Michael C Moon, MD, Katerina Molnar,

Morphologic characteristics of varicose veins: possible role of metalloproteinases Kenneth J Woodside, MD, Mingdao Hu, MD, Ann Burke, MS, Maki Murakami,

Transduction of peptide analogs of the small heat shock–related protein HSP20 inhibits intimal hyperplasia Deron J Tessier, MD, Padmini Komalavilas,

David K.W. Chew, MD, Michael S. Conte, MD, Raouf A. Khalil, MD, PhD

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.

Mostafa N. El-Sanadiki, MB, MS, K. Simon Cross, MB, John J

Surgical Preparation Abolishes Endothelium-Derived Hyperpolarizing Factor-Mediated Hyperpolarization in the Human Saphenous Vein Jian-An Yang, MD, Guo-Wei.

Michael E. Landis, MDa, Edward C

Diabetes mellitus and experimental vein graft structure and function

Zeljko S. Radic, MD, Martin K. O'Donohoe, MB, FRCSI, Lewis B

Immunosuppressive treatment of aortic allografts

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,

Potential role of vacuolar H+–adenosine triphosphatase in neointimal formation in cultured human saphenous vein Hajime Otani, MDa, Hideyasu Ohmiya, MDa,

Matrix metalloproteinase 2–induced venous dilation via hyperpolarization and activation of K+ channels: Relevance to varicose vein formation Joseph D.

Tissue inhibitor of metalloproteinase-1 is increased in the saphenofemoral junction of patients with varices in the leg Jose R. Parra, MD, Robert A.

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

Brilliant blue FCF is a nontoxic dye for saphenous vein graft marking that abrogates response to injury Kyle M. Hocking, PhD, Weifeng Luo, PhD, Fan Dong.

Remodeling of experimental arteriovenous fistula with increased matrix metalloproteinase expression in rats Chih-Yang Chan, MD, Yih-Sharng Chen, MD,

Presentation transcript:

Dipeptidyl peptidase 4 inhibitor reduces intimal hyperplasia in rabbit autologous jugular vein graft under poor distal runoff Akio Koyama, MD, Kimihiro Komori, MD, PhD, Ryo Otsuka, RPT, Ms, Junko Kajikuri, PhD, Takeo Itoh, PhD Journal of Vascular Surgery Volume 63, Issue 5, Pages 1360-1370 (May 2016) DOI: 10.1016/j.jvs.2014.12.048 Copyright © 2016 Society for Vascular Surgery Terms and Conditions

Fig 1 Effects of vildagliptin on morphometric changes in autologous vein grafts, as assessed at 28 days after the operation. A and B, Microscopic findings revealed by elastica van Gieson staining in control group (A) and vildagliptin group (B). The inner (white) arrowhead indicates internal elastic lamina; the outer (yellow) arrowhead shows external elastic lamina. C-F, Morphometric analysis for lumen area (C), intimal thickness (D), medial thickness (E), and intima/media index (F) (n = 4, control group; n = 5, vildagliptin group). Four sections were obtained from each vein graft, and each section was stained by the elastica van Gieson method. The intimal thickness was measured at eight randomly selected different sites per section, and these values were averaged. The four sections were each examined in the same way, and the values were averaged to represent intimal hyperplasia in that graft. The extent of intimal hyperplasia was expressed as an intima/media index (intima thickness divided by media thickness). Results are expressed as values for individual grafts and as mean ± standard error of the mean (error bars). ∗P < .05, ∗∗P < .01, ∗∗∗P < .001 vs control group. Measurements were made by blinded researchers who were not otherwise involved in the present study. Journal of Vascular Surgery 2016 63, 1360-1370DOI: (10.1016/j.jvs.2014.12.048) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

Fig 2 Effects of vildagliptin on endothelial cell Ca2+ concentration ([Ca2+]i) (A and B) and vascular smooth muscle cell (VSMC) membrane potential (C and D) in vein grafts. Neither the basal [Ca2+]i (A) nor the resting membrane potential (C) in the vildagliptin group was significantly different from that in the control group. Acetylcholine (ACh, 3 μM) had no effect on endothelial cell [Ca2+]i (B) or VSMC membrane potential (D) in either the control or vildagliptin group. [Ca2+]i is expressed as the Fura-2 ratio (F340/F380). Data are shown as mean ± standard error of the mean (n = 4, in each case). Journal of Vascular Surgery 2016 63, 1360-1370DOI: (10.1016/j.jvs.2014.12.048) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

Fig 3 Effects of vildagliptin on resting membrane potential and 5-hydroxytryptamine (5-HT)-induced depolarization in vascular smooth muscle cells (VSMCs) in vein grafts. A and B, Actual traces of 5-HT (0.1 μM)-induced depolarization in control group (A) and vildagliptin group (B). C, Resting VSMC membrane potential. D, 5-HT (0.1 μM)-induced depolarization in VSMCs. Data are shown as mean ± standard error of the mean (n = 4, in each case). Journal of Vascular Surgery 2016 63, 1360-1370DOI: (10.1016/j.jvs.2014.12.048) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

Fig 4 Effects of vildagliptin on acetylcholine (ACh)-induced endothelium-dependent relaxation in vein grafts. A, Effects of ACh (30 nM to 10 μM) on the contraction induced by prostaglandin F2α (PGF2α) in endothelium-intact preparations [E(+)] from control group (n = 4) and vildagliptin group (n = 6) and also in endothelium-denuded preparations [E(−)] from vildagliptin group (n = 5). B, Effects of Nω-nitro-l-arginine (l-NNA) on ACh-induced response in endothelium-intact preparations from vildagliptin group. After ACh-induced responses had been recorded before application of l-NNA [l-NNA(−)], l-NNA was applied for 60 minutes, and ACh-induced responses were again obtained in the presence of l-NNA [l-NNA(+)] (n = 3). The concentration of PGF2α was adjusted to obtain similar amplitudes of contraction before and after application of l-NNA (Table I). The contraction induced by PGF2α before application of ACh was normalized as a relative tension of 1.0 for each preparation. Data are shown as mean ± standard error of the mean. ∗∗∗P < .001 vs vildagliptin group E(+), †††P < .001 vs l-NNA(−). Journal of Vascular Surgery 2016 63, 1360-1370DOI: (10.1016/j.jvs.2014.12.048) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

Fig 5 Effects of Nω-nitro-l-arginine (l-NNA) on the contractions induced by high K+ and 5-hydroxytryptamine (5-HT) in vein grafts. A and B, Actual traces recorded from endothelium-intact vein grafts from control group (A) and vildagliptin group (B). After the responses induced by high K+ (128 mM) and 5-HT (10 nM to 10 μM) had been recorded, l-NNA (0.1 mM) was applied for 60 minutes and high K+ and 5-HT were again applied in the presence of l-NNA. 5-HT was applied at concentrations of (1) 10 nM, (2) 30 nM, (3) 0.1 μM, (4) 0.3 μM, (5) 1 μM, (6) 3 μM, and (7) 10 μM. C and D, Absolute tension induced by 128 mM K+ (C) or 10 μM 5-HT (D) before [l-NNA(−)] and after [l-NNA(+)] application of l-NNA in endothelium-intact [E(+)] or endothelium-denuded [E(−)] preparations in control group (black, n = 4) and vildagliptin group (red, n = 4). ∗P < .05 vs l-NNA(−). E and F, Summary of the effects of l-NNA on 5-HT-induced contraction in endothelium-intact [E(+)] or endothelium-denuded [E(-)] preparations in control group (E, n = 4) and vildagliptin group (F, n = 4). Data are shown as mean ± standard error of the mean. ∗P < .05, ∗∗∗P < .001 vs l-NNA(−). Journal of Vascular Surgery 2016 63, 1360-1370DOI: (10.1016/j.jvs.2014.12.048) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

Fig 6 Rate of relaxation after removal of 10 μM 5-hydroxytryptamine (5-HT) or 128 mM K+. Endothelium-denuded preparations were treated with 5-HT (n = 3, A) or high K+ (n = 4, B) to obtain the maximum contraction, followed by rapid washout to induce relaxation. Tension was normalized to the maximum tension in each case. Time required for half-relaxation for 5-HT (C) and high K+ (D). Data are shown as mean ± standard error of the mean. ∗P < .05 vs “Control.” Journal of Vascular Surgery 2016 63, 1360-1370DOI: (10.1016/j.jvs.2014.12.048) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

Fig 7 Histologic images of elastica van Gieson (A and B) and Masson trichrome (C and D) staining in vein grafts from control group (A and C) and vildagliptin group (B and D). Similar observations were made in three other preparations. E, Area occupied by collagen within intima/media was calculated and is shown as a percentage of the total intima/media area. The measurement was made at eight randomly selected different sites per section, and these values were averaged. The four sections were each examined in the same way, and the values were averaged for that graft. Data are shown as mean ± standard error of the mean for four samples from each group. *P < .05 vs “Control.” Measurements were made by blinded researchers who were not otherwise involved in the present study. Journal of Vascular Surgery 2016 63, 1360-1370DOI: (10.1016/j.jvs.2014.12.048) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

Fig 8 Immunohistochemical staining of matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 2 (TIMP-2) in vein grafts from control group (left panel) and vildagliptin group (right panel). A-D, DAB staining: (A) negative control staining without primary antibody; (B) TIMP-2 staining; (C) MMP-9 staining; (D) MMP-2 staining. Expressions of TIMP-2 and MMP-9 were not apparently different between the two groups, but that of MMP-2 was apparently less in the vildagliptin group than in the control group. Similar observations were made in three other preparations. E, Immunofluorescence intensities for MMP-2 were detected by confocal laser scanning microscopy. F, Summary of the immunofluorescence results. The measurement was made at eight randomly selected different sites per section, and these values were averaged. The four sections were each examined in the same way, and the values were averaged for that graft. Data are shown as mean ± standard error of the mean for four samples from each group. *P < .05 vs “Control.” Measurements were made by blinded researchers who were not otherwise involved in the present study. Journal of Vascular Surgery 2016 63, 1360-1370DOI: (10.1016/j.jvs.2014.12.048) Copyright © 2016 Society for Vascular Surgery Terms and Conditions