Gene therapy in peripheral artery disease

Sanada, Fumihiro; Taniyama, Yoshiaki; Kanbara, Yasuhiro; Otsu, Rei; Ikeda-Iwabu, Yuka; Carracedo, Miguel; Rakugi, Hiromi; Morishita, Ryuichi

doi:10.1517/14712598.2015.1007039

Cited by 26 publications

(16 citation statements)

References 90 publications

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“…HGF, a promising biomarker for CHD, is released into the bloodstream following the damage of endothelial cells [24]. In addition, HGF has been shown to attenuate chronic tissue damage, promote angiogenesis, inhibit brosis and apoptosis, regulate in ammation and improve prognosis [25,26] in various ischemic disease models such as MI [27] and peripheral arterial occlusive disease (PAOD) [28]. The biological function of HGF is mediated by its unique tyrosine kinase receptor c-Met [29], and the activation of c-Met receptor further activates many intracellular signaling pathways including RASmitogen activated protein kinase (MAPK), signal transducer and activator of transcription (STAT), phosphatidylinositol-3 kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR) and β-catenin pathway [30][31][32].…”

Section: Discussionmentioning

confidence: 99%

HGF Treatment Promotes Cardiac Function and Cardiac Repair: Meta-analysis of Pig Models With Myocardial Infarction

Chen

Wang

et al. 2020

Preprint

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Background: Previous studies reported that hepatocyte growth factor (HGF) could promote angiogenesis and cardiac function after myocardial infarction (MI) in pigs. However, the results of these studies were controversial. To clarify the therapeutic efficacy of local HGF administration after MI, we performed a systematic review and meta-analysis of data from the pig models, which could provide evidence for the feasibility of clinical HGF application.Methods: PubMed, EMBASE, and China National Knowledge Infrastructure were searched for randomized studies that correspond to our subject. The search terms included (hepatocyte growth factor OR HGF) AND (heart failure OR HF OR myocardial infarction OR MI OR AMI OR coronary heart disease OR CHD). The primary endpoint indicators were identified as the left ventricular ejection fraction (LVEF) and capillaries density. Other parameters reflecting cardiac function and ventricular remodeling were analyzed as secondary indicators, including ventricular volume, infarct size, apoptotic index and others.Results: In total, 9 studies were finally included in the meta-analysis. On comparing the cardiac function indexes, the HGF group was found to be better than the control group in regard to LVEF, stroke volume, left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV). However, no statistically significant differences were found in heart rate. Furthermore, HGF treatment promotes angiogenesis in ischemic areas, which is manifested by increased capillary density. In addition, the HGF group was found to be better than the control group when it comes to infarct size, arteriole densities, and other indicators of cardiac remodeling.Conclusions: HGF treatment can effectively promote cardiac function and cardiac repair including angiogenesis, and this strategy is a promising cardio-protective approach that merits further clinical studies.

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Section: Discussionmentioning

confidence: 99%

HGF Treatment Promotes Cardiac Function and Cardiac Repair: Meta-analysis of Pig Models With Myocardial Infarction

Chen

Wang

et al. 2020

Preprint

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“…HGF and its potential angiogenic, anti-apoptotic, and anti-brotic effects [27,28] have been extensively studied in various models of ischaemic disease, such as MI [29] and peripheral artery occlusion disease [30]. A Phase III clinical trial of intramuscular injection of plasmid HGF for the treatment of severe limb ischaemia has been successful [31], suggesting that HGF may also be used for the treatment of IHD.…”

Section: Discussionmentioning

confidence: 99%

Gene Therapy with Hepatocyte Growth Factor Improves Left Ventricular Systolic Function After Myocardial Infarction: A Systematic Review and Meta-analysis of Pig Models

Du¹,

Chen²,

Wang³

et al. 2020

Preprint

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Background: Hepatocyte growth factor (HGF) is an angiogenic cytokine which can promote angiogenesis and inhibit fibrosis. Previous studies have shown that HGF may have significant therapeutic effects on ischaemic diseases, such as ischaemic heart disease and peripheral arterial occlusive disease. Due to insufficient clinical study evidence, we conducted a quantitative meta-analysis of HGF therapy in pigs with myocardial infarction (MI) to provide more reliable evidence for the feasibility and effectiveness of HGF therapy for MI patients. We also analysed the efficacy and characteristics of different gene therapy vectors and drug delivery routes.Methods: PubMed, EMBASE, and the China National Knowledge Infrastructure were searched for randomised studies that corresponded to our subject. The search terms included (hepatocyte growth factor OR HGF) AND (heart failure OR HF OR myocardial infarction OR MI OR AMI OR coronary heart disease OR CHD). The retrieved articles were screened strictly according to the inclusion criteria. The endpoints were the left ventricular ejection fraction (LVEF) and capillary density in the ischaemic regions in the model pigs.Results: A total of nine studies were eventually included in this meta-analysis. Our analysis showed that LVEF (with mean difference [MD]:9.73, 95%CI :8.70, 10.76, P < 0.00001) and capillary density (MD:79.98, 95%CI :24.58,135.39, P=0.005) in the HGF group were significantly higher than those in the control group several weeks after HGF treatment. Further analysis showed that there was no statistically significant difference in the improvement of LVEF caused by intracoronary adenovirus5-mediated HGF (Ad5-HGF) gene transfer and intramyocardial plasmid HGF injection (12.63±3.2 vs 9.4±1.09, P=0.06), while intramyocardial injection of plasmid HGF had a stronger angiogenic capacity than intramyocardial administration of Ad5-HGF and HGF in hydrogel (117.34±27.82 vs 26.45±22.11 vs 11.50±5.28, P＜0.00001).Conclusions: HGF therapy can effectively promote angiogenesis and recovery of cardiac function and is a promising cardiac repair method. Intracoronary Ad5 vector transfer and intramyocardial injection of plasmid vectors can be used as effective means of gene therapy, and hydrogel as a vector also has potential applications.

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“…8,74 The ability to noninvasively evaluate the biodistribution of transplanted cells should be achievable through the utilization of high-sensitivity PET and SPECT imaging of radiolabeled cells (~10 4 – 10 6 cells/voxel). 75 Multiple clinical trials have already demonstrated the feasibility of tracking effective cell delivery in the myocardium of patients following myocardial infarction.…”

Section: Potential For Application Of Novel Radionuclidesmentioning

confidence: 99%

“…In addition to endovascular procedures, systemic treatments such as antiplatelet and cholesterol lowering drugs, as well as renin-angiotensin system inhibitors, have been applied for the treatment of PVD patients who are not candidates for revascularization due to multiple diffuse stenosis or arterial calcification. 8 Gene-based therapies using growth factors such as vascular endothelial growth factor (VEGF), 9 fibroblast growth factor (FGF), 10 hepatocyte growth factor (HGF), 11 and hypoxia inducible factor 1 (HIF-1) 12 have also gained attention in recent years. Additionally, cell-based therapies for PVD have been assessed using endothelial progenitor cells (EPCs), 13 bone marrow mononuclear cells (BM-MNCs), 14 and mesenchymal stem cells (MSCs) 15 and demonstrated relative benefits.…”

Section: Introductionmentioning

confidence: 99%

Novel Applications of Radionuclide Imaging in Peripheral Vascular Disease

Stacy

Sinusas

2016

Cardiology Clinics

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Peripheral vascular disease (PVD) is a progressive atherosclerotic disease that leads to stenosis or occlusion of blood vessels supplying the lower extremities. Current diagnostic imaging techniques commonly focus on evaluation of anatomy or blood flow at the macrovascular level and do not permit assessment of the underlying pathophysiology associated with disease progression or treatment response. Molecular imaging with radionuclide-based approaches, such as PET and SPECT, can offer novel insight into PVD by providing non-invasive assessment of biological processes such as angiogenesis and atherosclerosis. This review discusses emerging radionuclide-based imaging approaches that have potential clinical applications in the evaluation of PVD progression and treatment.

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Gene therapy in peripheral artery disease

Abstract: Compared with VEGF and FGF, HGF has a unique molecular effect on inflammation, fibrosis and cell senescence under pathological conditions. These features may explain the clinical benefits of HGF in PAD patients.

Cited by 26 publications

References 90 publications

HGF Treatment Promotes Cardiac Function and Cardiac Repair: Meta-analysis of Pig Models With Myocardial Infarction

HGF Treatment Promotes Cardiac Function and Cardiac Repair: Meta-analysis of Pig Models With Myocardial Infarction

Gene Therapy with Hepatocyte Growth Factor Improves Left Ventricular Systolic Function After Myocardial Infarction: A Systematic Review and Meta-analysis of Pig Models

Novel Applications of Radionuclide Imaging in Peripheral Vascular Disease

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