Arterial Gene Therapy for Therapeutic Angiogenesis in Patients With Peripheral Artery Disease

Circulation ◽  
1995 ◽  
Vol 91 (11) ◽  
pp. 2687-2692 ◽  
Author(s):  
Jeffrey M. Isner ◽  
Kenneth Walsh ◽  
James Symes ◽  
Ann Pieczek ◽  
Satoshi Takeshita ◽  
...  
VASA ◽  
2007 ◽  
Vol 36 (3) ◽  
pp. 165-173 ◽  
Author(s):  
Nikol

Peripheral artery disease is a highly prevalent disease which is characterised by a high unmet medical need particularly in the more advanced stages of disease. Recent advances in the knowledge of the complex regulation of angiogenesis and arteriogenesis and ways to its induction offer hope for a novel strategy that is based on the generation of such new vessels. This strategy termed "therapeutic angiogenesis" is a concept based on the use of angiogenic factors or stem cells or their combination to promote neovascularisation for the treatment of ischaemic tissues. This article reviews both regulation of angiogenesis and the development of therapeutic strategies based on this knowledge using gene therapy. This includes knowledge from animal experiments as well as from phase I and phase II clinical trials. This information may be particularly important at a time when angiogenesis gene therapy enters the stage of phase III clinical testing hopefully leading to the first time approval of this completely new class of drug in the near future. Following articles of this series will review therapeutic angiogenesis approaches based on cytokine therapy and stem cell therapy.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Munehisa Shimamura ◽  
Hironori Nakagami ◽  
Hiroshi Koriyama ◽  
Ryuichi Morishita

Gene therapy and cell-based therapy have emerged as novel therapies to promote therapeutic angiogenesis in critical limb ischemia (CLI) caused by peripheral artery disease (PAD). Although researchers initially focused on gene therapy using proangiogenic factors, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factors (HGF), cell therapy using bone marrow mononuclear cells (BMMNCs), mesenchymal stem cells (BMMSCs), G-CSF-mobilized peripheral blood mononuclear cells (M-PBMNCs), and endothelial progenitor cells (EPCs) have also been extensively studied. Based on the elaborate studies and favorable results of basic research, some clinical phase I/II trials have been performed, and the results demonstrate the safety of these approaches and their potential for symptomatic improvement in CLI. However, the phase 3 clinical trials have thus far been limited to gene therapy using the HGF gene. Further studies using well-designed larger placebo-controlled and long-term randomized control trials (RCTs) will clarify the effectiveness of gene therapy and cell-based therapy for the treatment of CLI. Furthermore, the development of efficient gene transfer systems and effective methods for keeping transplanted cells healthy will make these novel therapies more effective and ease the symptoms of CLI.


2017 ◽  
pp. 133-144 ◽  
Author(s):  
Jun Muratsu ◽  
Fumihiro Sanada ◽  
Yoshiaki Taniyama ◽  
Yuka Ikeda-Iwabu ◽  
Rei Otsu ◽  
...  

2012 ◽  
Vol 17 (3) ◽  
pp. 174-192 ◽  
Author(s):  
Geoffrey O Ouma ◽  
Rebecca A Jonas ◽  
M Haris U Usman ◽  
Emile R Mohler

2004 ◽  
Vol 4 (3) ◽  
pp. 295-300 ◽  
Author(s):  
G. Melillo ◽  
F. Serino ◽  
C. Cirielli ◽  
M. Capogrossi

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Mahesh Thirunavukkarasu ◽  
Inam A Shaikh ◽  
Vaithinathan Selvaraju ◽  
J.Alexandar Palesty ◽  
Nilanjana Maulik

Introduction: Peripheral artery disease affects 12-20% Americans over the age of 60. Thioredoxin-1 (Trx-1) is a class of small redox proteins. We have demonstrated earlier that Trx-1 reduces oxidative stress resulting in less inflammation and increased angiogenesis in cardiac muscle via heme oxygenase-1 (HO-1) and VEGF after myocardial infarction. In the current study, we evaluate the effect of Trx-1 on post-ischemic hindlimb recovery. Methods: Peripheral artery disease was mimicked using a hindlimb ischemia (HLI) model. Wild type (WT) and Trx-1 transgenic (Trx-1Tg/+) mice (8-12 weeks old) were subjected to femoral artery ligation. Following surgery, mice were observed for 5 weeks. Serial laser doppler images were obtained, and perfusion ratios between the ischemic and non-ischemic limbs were calculated at set time intervals. The perfusion ratios were compared between WT and Trx-1Tg/+ groups. Immunohistochemical analysis of the skeletal muscle was performed to quantify the extent of fibrosis, capillary and arteriolar density 35 days after surgery. In addition, another set of experiments was designed with Ad.Trx-1 gene therapy after femoral artery ligation to study the molecular mechanism of neovascularization with Trx-1. Results: The recovery of hind limb perfusion was significantly increased in Trx-1Tg/+ mice at day 7 (0.19 ± 0.03 vs. 0.36 ± 0.07 (n=12-9), day-21 (0.37 ± 0.05 vs. 0.62 ± 0.03 (n=12-9), and day 28 (0.40 ± 0.04 vs. 0.79 ± 0.04 (n=10-9); p<0.05). Capillary density [1265 ± 87.8 vs. 762.4 ± 86.6 counts/mm2 ; (n=5); p<0.05] and arteriolar density [36.2 ± 2.96 vs. 22± 1.33 counts/mm2 ; (n=5); p<0.05] staining showed significant increase in Trx-1Tg/+ mice as compared to WT mice. Picrosirrus Red and immunofluorescence staining showed decreased fibrosis [8.3 ± 0.46 vs. 22.2 ± 1.04 (n=5); p<0.0001] and increased HO-1 expression respectively in Trx-1Tg/+ mice group as compared to WT mice, respectively. Trx-1 gene therapy study also revealed by Western blot analysis, increased Trx-1 (4.2 fold) and HO-1 (8.2 fold) expression in Ad.Trx-1-HLI as compared to Ad.LacZ-HLI. Conclusions: Our results suggest that Trx-1 is a potential therapeutic agent to increase blood perfusion and angiogenesis for the treatment of critical limb ischemia patients.


Gene ◽  
2013 ◽  
Vol 525 (2) ◽  
pp. 220-228 ◽  
Author(s):  
Anna Grochot-Przeczek ◽  
Jozef Dulak ◽  
Alicja Jozkowicz

2004 ◽  
Vol 36 (4) ◽  
pp. 336-344 ◽  
Author(s):  
Hyun-Joong Kim ◽  
Shin Yi Jang ◽  
Joong-Il Park ◽  
Jonghoe Byun ◽  
Dong-Ik Kim ◽  
...  

2015 ◽  
Vol 15 (3) ◽  
pp. 381-390 ◽  
Author(s):  
Fumihiro Sanada ◽  
Yoshiaki Taniyama ◽  
Yasuhiro Kanbara ◽  
Rei Otsu ◽  
Yuka Ikeda-Iwabu ◽  
...  

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