VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond

Giacca, Mauro; Zacchigna, Serena

doi:10.1038/gt.2012.17

Cited by 225 publications

(157 citation statements)

References 93 publications

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“…35,36 The VEGF signaling pathway is now used as a target pathway for treatment of ischemic cardiovascular disease. 37,38 It is reported that TGFb signaling pathway is a risk factor for cardiovascular disease 39 and has an important role in the development of myocardial infarction. 40,41 To demonstrate that replication of the results of pathways in independent samples is much easier than replication of genes, we plotted in Figure 4 where the genes with red and blue color were mildly associated with EOMI in the EA and AA populations, respectively, and the genes with green color were mildly associated with EOMI in both of the EA and AA population (see data presented in Supplementary Table 1).…”

Section: Application To a Real Data Examplementioning

confidence: 99%

Pathway analysis with next-generation sequencing data

et al. 2014

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Although pathway analysis methods have been developed and successfully applied to association studies of common variants, the statistical methods for pathway-based association analysis of rare variants have not been well developed. Many investigators observed highly inflated false-positive rates and low power in pathway-based tests of association of rare variants. The inflated false-positive rates and low true-positive rates of the current methods are mainly due to their lack of ability to account for gametic phase disequilibrium. To overcome these serious limitations, we develop a novel statistic that is based on the smoothed functional principal component analysis (SFPCA) for pathway association tests with next-generation sequencing data. The developed statistic has the ability to capture position-level variant information and account for gametic phase disequilibrium. By intensive simulations, we demonstrate that the SFPCA-based statistic for testing pathway association with either rare or common or both rare and common variants has the correct type 1 error rates. Also the power of the SFPCA-based statistic and 22 additional existing statistics are evaluated. We found that the SFPCA-based statistic has a much higher power than other existing statistics in all the scenarios considered. To further evaluate its performance, the SFPCA-based statistic is applied to pathway analysis of exome sequencing data in the early-onset myocardial infarction (EOMI) project. We identify three pathways significantly associated with EOMI after the Bonferroni correction. In addition, our preliminary results show that the SFPCA-based statistic has much smaller P-values to identify pathway association than other existing methods.

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Section: Application To a Real Data Examplementioning

confidence: 99%

Pathway analysis with next-generation sequencing data

et al. 2014

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“…HIF-1α can directly influence the expression of VEGF and eNOS [16,17]. VEGF, an endothelial-specific mitogen and survival factor, is one of the most potent angiogenic factors, and is a key factor for both angiogenesis and vasculogenesis [18] eNOS can be activated in phosphorylation of serine 1177 residue and this triggers migration and angiogenesis [19,20].…”

Section: Discussionmentioning

confidence: 99%

Traditional Chinese medicine Tongxinluo stimulates coronary collateral growth in a pig myocardial infarction model

Wang¹,

Ye²,

Cui³

et al. 2017

Hematol Med Oncol

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Coronary collaterals were reported improving symptoms as well as prognosis for patients with coronary artery disease. This study aimed to investigate whether traditional Chinese medicine Tongxinluo could stimulate coronary collateral growth in a pig acute myocardial infarction (AMI) model. The AMI model was established by surgically ligation of left anterior descending coronary artery (LAD). Twenty-one Chinese Suzhong pigs were randomly divided into two control groups and two treatment groups taking Tongxinluo of 0.36g.kg -1.d -1 and 0.72g.kg -1 .d -1 respectively. Coronary artery angiography (CAG) and left ventriculography were performed to evaluate collaterals and cardiac function 1 month after the treatment, and the density of collateral capillaries of myocardial samples was also counted. The plasma levels of nitric oxide (NO) and endothelin-1 (ET-1) were serially determined. The density of capillaries was significantly higher in both low-dose and high-dose Tongxinluo groups than that in the negative control (P < 0.01) and the positive control groups (P < 0.05). Grade III collateral circulation was found in both treatment groups one month after LAD ligation, and the grades of collateral circulations were positively correlated to the Tongxinluo dosages (P = 0.0191). The cardiac function, the plasma levels of NO and ET-1 showed no significant difference among the treatment and positive control groups. This study demonstrated that Tongxinluo stimulates coronary collateral growth in a pig AMI model.

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“…14 However, in spite of plausibility of the approach in provoking new vessel formation and alleviating tissue ischemia, direct delivery of angiogenic factors via gene and cell therapy or protein delivery to the myocardium or peripheral tissues has thus far been unsuccessful clinically. 15,16 Identification of resident and circulating vascular progenitor cells has shifted the emphasis from direct delivery of the angiogenic factors toward harnessing the therapeutic potentials of vascular progenitor cells in angiogenesis. Induced pluripotent stem cells (iPSCs), generated upon expression of a defined set of transcription factors in differentiated cells, 17 as well as bone marrow derived mesenchymal stem cells have been successfully applied in experimental models of angiogenesis.…”

Section: E256 Circulation Researchmentioning

confidence: 99%

Circulation Research Thematic Synopsis

2012

Circulation Research

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Circulation Research Thematic Synopses:The goal of Thematic Synopses is to provide our readers with a concise but comprehensive overview of the work published in Circulation Research, which we hope will keep our readers abreast of recent scientific discoveries and facilitate discussion, interpretation, and integration of the findings. These collections of articles are organized thematically and the papers listed in chronological order, beginning with the most recent ones. In each synopsis, the top downloaded original research articles (normalized to time since publication) are highlighted in yellow. Review articles are also included with titles highlighted in blue and the summary of each is provided. Instead of using abstracts, we have elected to publish the Novelty and Significance section of each article, which we believe provides a clear précis of the salient findings and their implications in a language that is easily understandable by the non-initiated. This will enable readers who are not experts in a particular field to grasp the significance and impact of work performed in other fields. It is our hope and expectation that Thematic Synopses will help readers to gain a broader awareness and a deeper understanding of the status of research across the vast landscape of cardiovascular research. Moreover, the signaling cascades that regulate the responses to external and internal stimuli including response to autonomic outflow from the hypothalamic region and the neurotransmitters are well characterized. Furthermore, vascular microRNA and non-coding RNAs have emerged as major regulators of vessel wall homeostasis and pathologies. [5][6][7][8][9][10][11][12][13] These molecular networks are currently being investigated as specific targets for interventions to prevent and assuage vascular diseases. Since identification of the first specific angiogenic molecule by Folkman and colleagues in 1971, a large number of proangiogenic factors have been identified and characterized. 14 However, in spite of plausibility of the approach in provoking new vessel formation and alleviating tissue ischemia, direct delivery of angiogenic factors via gene and cell therapy or protein delivery to the myocardium or peripheral tissues has thus far been unsuccessful clinically. 15,16 Identification of resident and circulating vascular progenitor cells has shifted the emphasis from direct delivery of the angiogenic factors toward harnessing the therapeutic potentials of vascular progenitor cells in angiogenesis. Induced pluripotent stem cells (iPSCs), generated upon expression of a defined set of transcription factors in differentiated cells, 17 as well as bone marrow derived mesenchymal stem cells have been successfully applied in experimental models of angiogenesis. [18][19][20][21] Nevertheless, the field is in the early stages of its evolution. New approaches are being developed and applied to enhance angiogenesis either through delivery of vascular stem cells alone or in conjunction with angiogenic factors. Understanding the fundam...

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VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond

Cited by 225 publications

References 93 publications

Pathway analysis with next-generation sequencing data

Pathway analysis with next-generation sequencing data

Traditional Chinese medicine Tongxinluo stimulates coronary collateral growth in a pig myocardial infarction model

Circulation Research Thematic Synopsis

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