Vascular endothelial growth factor gene transfer therapy for coronary artery disease: A systematic review and meta‐analysis

Yuan, Rong; Xin, Qiqi; Shi, Weili; Liu, Wei; Lee, Simon Ming‐Yuen; Hoi, Maggie Pui Man; Li, Lin; Zhao, Jun; Cong, Weihong; Chen, Ke-ji

doi:10.1111/1755-5922.12461

Cited by 13 publications

(9 citation statements)

References 38 publications

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“…Other studies showed that miR-214/361-5p were able to suppress VEGF expression and endothelial progenitor cell angiogenic activity [ 67 , 68 ]. Moreover, VEGF gene therapy is one of the safe and effective treatments in case of a cardiac event [ 69 ]. Furthermore, atorvastatin is one of the treatments for dyslipidemia and has been demonstrated to prevent cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

Study of the Association between VEGF Polymorphisms and the Risk of Coronary Artery Disease in Koreans

Kim

Lee

et al. 2022

JPM

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Coronary artery disease (CAD), a leading cause of death worldwide, has a complex etiology comprising both traditional risk factors (type 2 diabetes, dyslipidemia, arterial hypertension, and cigarette smoking) and genetic factors. Vascular endothelial growth factor (VEGF) notably contributes to angiogenesis and endothelial homeostasis. However, little is known about the relationship between CAD and VEGF polymorphisms in Koreans. The aim of this study is to investigate the associations of 2 VEGF promoter region polymorphisms (−1154G>A [rs1570360], −1498T>C [rs833061]) and 4 VEGF 3′-UTR polymorphisms (+936C>T [rs3025039], +1451C>T [rs3025040], +1612G>A [rs10434], and +1725G>A [rs3025053]) with CAD susceptibility in Koreans. We studied 885 subjects: 463 CAD patients and 422 controls. Genotyping was conducted with polymerase chain reaction-restriction fragment length polymorphism analysis and TaqMan allelic discrimination assays, and the genotype frequencies were calculated. We then performed haplotype and genotype combination analyses and measured the associations between VEGF polymorphisms and clinical variables in both the CAD patients and control subjects. We detected statistically significant associations between CAD and certain VEGF allele combinations. In the haplotypes of 5 single-nucleotide polymorphisms, the VEGF allele combination −1154A/+936T was associated with a decreased prevalence of CAD (A-T-T-G-G of VEGF −1154G>A/−1498T>C/+936C>T/+1612G>A/+1725G>A, AOR = 0.077, p = 0.021). In contrast, the VEGF allele combinations −1498T/+1725A and −1498T/+1612A/+1725A were associated with an increased prevalence of CAD (G-T-C-C-A of VEGF −1154G>A/−1498T>C/+936C>T/+1451C>T/+1725G>A, AOR = 1.602, p = 0.047; T-C-C-A-A of VEGF −1498T>C/+936C>T/+1451C>T/+1612G>A/+1725G>A, AOR = 1.582, p = 0.045). Gene–environment combinatorial analysis showed that the combination of the VEGF +1725AA genotype and several clinical factors (e.g., body mass index, hemoglobin A1c, and low-density lipoprotein cholesterol) increased the risk of CAD. Therefore, we suggest that VEGF polymorphisms and clinical factors may impact CAD prevalence.

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Section: Discussionmentioning

confidence: 99%

Study of the Association between VEGF Polymorphisms and the Risk of Coronary Artery Disease in Koreans

Kim

Lee

et al. 2022

JPM

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“…11 Early-stage clinical trials of VEGF gene transfer in patients with nonrevascularizable, severe CAD, and/or severe angina have demonstrated a favorable safety profile, with several trials demonstrating improvements in myocardial perfusion and anginal symptoms. 11,70 However, there was significant heterogeneity between trials, including critical differences in method of administration and vectors used for gene transfer. Experience gained from these initial trials and additional preclinical research has greatly increased our understanding of gene therapy pharmacokinetics and the biological mechanisms of angiogenesis.…”

Section: Recent Developments In Angiogenic Therapymentioning

confidence: 99%

“…In addition, numerous clinical trials over 2 decades have demonstrated a uniformly favorable safety profile for these techniques. 70,[79][80][81][82] Continued preclinical research has also advanced our understanding of the molecular mechanisms of angiogenesis to further refine therapeutic applications of the VEGF gene family. The VEGF-A gene undergoes extensive alternative splicing, forming multiple isoforms with distinct biological properties.…”

Section: Recent Developments In Angiogenic Therapymentioning

confidence: 99%

“…83 Clinical trials to date have administered only a single VEGF-A isoform. 11,70 However, simultaneous administration of the 3 major isoforms (VEGF-121, -165, and -189) produces a synergistic effect, greatly increasing the in vivo angiogenic response compared with a single isoform. 83 The efficacy and safety of VEGF administration is further enhanced by encoding all 3 major isoforms in a single viral vector and modifying the introns to optimize the ratio of isoform expression.…”

Section: Recent Developments In Angiogenic Therapymentioning

confidence: 99%

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Clinical potential of angiogenic therapy and cellular reprogramming

2021

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Feature Editor Note-You're driving along the freeway during rush hour. You're running late and find yourself in bumper-to-bumper traffic. You have 3 options: (1) do nothing, suffer with anguish inside; (2) find productive ways to pass the time, like listen to a podcast or talk on the phone; or (3) get off on the next exit and find an alternative, roundabout path to your destination. Similarly, patients suffering from coronary artery disease can opt to do nothing; stop progression and treat their symptoms with medical therapy; or undergo revascularization either percutaneously or surgically.There are few options, however, for those who develop chronic coronary artery disease without suitable revascularization strategies. They have missed their exit and are stuck in this metaphorical traffic jam, with no radio and no cell phone. These patients may experience refractory angina or develop ischemic cardiomyopathy and heart failure. Exploring solutions to this increasingly widespread problem is imperative. Chronic heart failure is rising, while the number of organs available for transplantation remains limited. Similarly, bridge therapies such as ventricular assist devices are resource intensive and are typically only performed at select, high-volume institutions.

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“…Animal models of cardiac gene therapy by using intracellular plasmid delivery suggested benefits of such approaches, as adenoviral delivery of vascular endothelial growth factor (VEGF) increased myocardial perfusion in a porcine ischemic myocardium ( Hassinen et al, 2016 ). However, similar to cell-based clinical trials, cardiac gene therapy did not yet lead to a breakthrough in the treatment of chronic ischemic human heart ( Yuan et al, 2018 ). To achieve clinically relevant success, timing of delivery, type and source of genes for cardiac therapy, furthermore, tracking methods need to be optimized ( Grochot-Przeczek, Dulak, and Jozkowicz 2013 ; Scarfe et al, 2017 ; Tompkins et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Cell-Based HIF1α Gene Therapy Reduces Myocardial Scar and Enhances Angiopoietic Proteome, Transcriptomic and miRNA Expression in Experimental Chronic Left Ventricular Dysfunction

Gara

Ong

Winkler

et al. 2022

Front. Bioeng. Biotechnol.

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Recent preclinical investigations and clinical trials with stem cells mostly studied bone-marrow-derived mononuclear cells (BM-MNCs), which so far failed to meet clinically significant functional study endpoints. BM-MNCs containing small proportions of stem cells provide little regenerative potential, while mesenchymal stem cells (MSCs) promise effective therapy via paracrine impact. Genetic engineering for rationally enhancing paracrine effects of implanted stem cells is an attractive option for further development of therapeutic cardiac repair strategies. Non-viral, efficient transfection methods promise improved clinical translation, longevity and a high level of gene delivery. Hypoxia-induced factor 1α is responsible for pro-angiogenic, anti-apoptotic and anti-remodeling mechanisms. Here we aimed to apply a cellular gene therapy model in chronic ischemic heart failure in pigs. A non-viral circular minicircle DNA vector (MiCi) was used for in vitro transfection of porcine MSCs (pMSC) with HIF1α (pMSC-MiCi-HIF-1α). pMSCs-MiCi-HIF-1α were injected endomyocardially into the border zone of an anterior myocardial infarction one month post-reperfused-infarct. Cell injection was guided via 3D-guided NOGA electro-magnetic catheter delivery system. pMSC-MiCi-HIF-1α delivery improved cardiac output and reduced myocardial scar size. Abundances of pro-angiogenic proteins were analyzed 12, 24 h and 1 month after the delivery of the regenerative substances. In a protein array, the significantly increased angiogenesis proteins were Activin A, Angiopoietin, Artemin, Endothelin-1, MCP-1; and remodeling factors ADAMTS1, FGFs, TGFb1, MMPs, and Serpins. In a qPCR analysis, increased levels of angiopeptin, CXCL12, HIF-1α and miR-132 were found 24 h after cell-based gene delivery, compared to those in untreated animals with infarction and in control animals. Expression of angiopeptin increased already 12 h after treatment, and miR-1 expression was reduced at that time point. In total, pMSC overexpressing HIF-1α showed beneficial effects for treatment of ischemic injury, mediated by stimulation of angiogenesis.

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Vascular endothelial growth factor gene transfer therapy for coronary artery disease: A systematic review and meta‐analysis

Abstract: Vascular endothelial growth factor gene therapy appears to be safe and effective regarding serious cardiac events, with greater benefit when using adenoviral vectors. This meta-analysis highlights the need for further exploration in these areas.

Cited by 13 publications

References 38 publications

Study of the Association between VEGF Polymorphisms and the Risk of Coronary Artery Disease in Koreans

Study of the Association between VEGF Polymorphisms and the Risk of Coronary Artery Disease in Koreans

Clinical potential of angiogenic therapy and cellular reprogramming

Cell-Based HIF1α Gene Therapy Reduces Myocardial Scar and Enhances Angiopoietic Proteome, Transcriptomic and miRNA Expression in Experimental Chronic Left Ventricular Dysfunction

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