Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction

Xia, Jing; Wu, Hai Yan; Lai, Bing Lin; Zheng, Li; Zhou, Deng Cheng; Chang, Zao Shang; Mao, Cheng Zhou; Liu, Guang Hui; Park, Kyu Sang; Zhao, Hui; Kim, Soo Ki; Song, Guo Hua; Cai, Dongqing; Qi, Xu

doi:10.1038/s41598-017-13547-1

Cited by 13 publications

(7 citation statements)

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“… 1 , 2 Acute myocardial infarction (AMI) can be thought of as a severe, even fatal type of ischemic cardiomyopathy. 3 , 4 Coronary artery acute occlusion leads to myocardial ischemia, hypoxia, and impaired energy supply, 5 leading acute imbalance of hemodynamics and cardiomyocyte irreversible damage. 6 The current treatments of acute myocardial infarction include thrombolysis and surgery.…”

Section: Introductionmentioning

confidence: 99%

<p>Screening and Identification of Potential Hub Genes in Myocardial Infarction Through Bioinformatics Analysis</p>

Xue

Qian

et al. 2020

CIA

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Background: Myocardial infarction (MI) is a common cause of death worldwide. It is characterized by coronary artery occlusion that causes ischemia and hypoxia of myocardial cells, leading to irreversible myocardial damage. Materials and Methods: To explore potential targets for treatment of MI, we reorganized and analyzed two microarray datasets (GSE4648 and GSE775). The GEO2R tool was used to screen for differentially expressed genes (DEGs) between infarcted and normal myocardium. We used the Database for Annotation, Visualization and Integrated Discovery (DAVID) to perform Gene Ontology functional annotation analysis (GO analysis) and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analysis (KEGG analysis). We examined protein-protein interactions to characterize the relationship between differentially expressed genes, and we screened potential hub genes according to the degree of connection. PCR and Western blotting were used to identify the core genes. Results: At different times of infarction, a total of 35 genes showed upregulation at all times; however, none of the genes showed downregulation at all 3 times. Similarly, 10 hub genes with high degrees of connectivity were identified. In vivo and in vitro experiments suggested that expression levels of MMP-9 increased at various times after myocardial infarction and that expression increased in a variety of cells simultaneously. Conclusion: Expression levels of MMP-9 increase throughout the course of acute myocardial infarction, and this expression has both positive and negative sides. Further studies are needed to explore the role of MMP-9 in MI treatment. The potential values of Il6,

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Section: Introductionmentioning

confidence: 99%

<p>Screening and Identification of Potential Hub Genes in Myocardial Infarction Through Bioinformatics Analysis</p>

Xue

Qian

et al. 2020

CIA

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“…In our experiments, IL‐19 treatment increased CD31‐positive capillaries at 7 days post‐MI. VEGF, acting through binding to its receptor VEGF receptor 2 and promoting endothelial cell survival, proliferation and migration, played a prominent role in post‐MI angiogenesis (Yang et al ., ; Xia et al ., ). In our experiments , IL‐19 treatment enhanced protein expression of VEGF in myocardium of mice with MI.…”

Section: Discussionmentioning

confidence: 97%

Exogenous IL‐19 attenuates acute ischaemic injury and improves survival in male mice with myocardial infarction

Zhang

et al. 2019

British J Pharmacology

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Background and purpose Myocardial infarction (MI) is one of the leading causes of death in China and often results in the development of heart failure. In this work, we tested the therapeutic role of Interleukin‐19 (IL‐19) in mice with MI and investigated the underlying molecular mechanism. Experimental approach Mice were subjected to MI by ligation of left anterior descending coronary artery (LAD) and treated with IL‐19 (10ng g‐1; i.p.). Key results Protein expression of IL‐19 and its receptor in myocardium were upregulated 24 hrs post‐MI in male mice. IL‐19 treatment decreased infarct and apoptosis in myocardium, accompanied by enhanced haem oxygenase‐1 (HO‐1) activities and reduced malondialdehyde (MDA) formation. Pretreatment with IL‐19 upregulated HO‐1 expression in cultured neonatal mouse ventricular myocytes and attenuated oxygen‐glucose deprivation (OGD)‐induced injuries in vitro. Furthermore, IL‐19 preserved cardiac function and improved survival of mice with MI. IL‐19 reduced inflammatory infiltrates and suppressed formation of TNF‐α, IL‐1β, and IL‐6. More importantly, IL‐19 inhibited polarization toward proinflammatory M1 macrophages and stimulated M2 macrophage polarization in myocardium of mice with MI. IL‐19 enhanced protein levels of vascular endothelial growth factor (VEGF) and promoted angiogenesis in myocardium of mice with MI. In addition, IL‐19 treatment increased DNA‐binding of the transcription factor STAT3 in myocardium of mice with MI. Conclusions and Implications Treatment with exogenous IL‐19 attenuated acute ischemic injury and improved survival of mice with MI. The mechanisms underlying these effects involved induction of HO‐1, M2 macrophage polarization, angiogenesis, and STAT3 activation.

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“…Apelin activates the myocyte enhancer factor 2 (MEF2) transcription factor in a Gα13 dependent manner to control myocardial infarct size and inflammation. ,, Apelin also stimulates the adaptive angiogenesis response by promoting nuclear translocation of hypoxia-inducible factor-1α (HIF-1α), which, in turn, upregulates VEGF . VEGF plays an important role in limiting myocardial infarct size as demonstrated by exogenous delivery of VEGF-A, which improved left ventricular contractile function after ischemic injury in animal models. , …”

Section: Discussionmentioning

confidence: 99%

“…38 VEGF plays an important role in limiting myocardial infarct size as demonstrated by exogenous delivery of VEGF-A, which improved left ventricular contractile function after ischemic injury in animal models. 51,52 The ERK5 signal transduction pathway has been implicated in cardiac contractility, maintenance of mitochondrial integrity, and ATP production. 53,54 Within this pathway, HCN exposure led to a decrease in expression of Map2k5 (encoding MEK5; fold change −2.2; p-value 8.77 × 10 −09 ), which is the exclusive upstream kinase to ERK5, 55,56 accompanied by decreased expression of Mef 2A, Mef 2C, and Creb2 (Figure 6B and Supplemental Table 2).…”

Section: ■ Discussionmentioning

confidence: 99%

Cyanide Poisoning Compromises Gene Pathways Modulating Cardiac Injury in Vivo

Lippner

Basi

et al. 2021

Chem. Res. Toxicol.

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Smoke inhalation from a structure fire is a common route of cyanide poisoning in the U.S. Cyanide inhibits cellular respiration, often leading to death. Its rapid distribution throughout the body can result in injuries to multiple organs, and cyanide victims were reported to experience myocardial infarction and other cardiac complications. However, molecular mechanisms of such complications are yet to be elucidated. While FDA-approved CN antidotes such as sodium thiosulfate and hydroxocobalamin are clinically used, they have foreseeable limitations during mass casualty situations because they require intravenous administration. To facilitate the development of better antidotes and therapeutic treatments, a global view of molecular changes induced by cyanide exposure is necessary. As an exploratory pursuit, we performed oligonucleotide microarrays to establish cardiac transcriptomes of an animal model of nose-only inhalation exposure to hydrogen cyanide (HCN), which is relevant to smoke inhalation. We also profiled cardiac transcriptomes after subcutaneous injection of potassium cyanide (KCN). Although the KCN injection model has often been used to evaluate medical countermeasures, this study demonstrated that cardiac transcriptomes are largely different from that of the HCN inhalation model at multiple time points within 24 h after exposure. Pathway analysis identified that HCN-induced transcriptomes were enriched with genes encoding mediators of pathways critical in modulation of cardiac complications and that a large number of such genes were significantly decreased in expression. We utilized the upstream regulatory analysis to propose drugs that can be potentially employed to treat cyanide-induced cardiac complications.

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Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction

Cited by 13 publications

References 50 publications

<p>Screening and Identification of Potential Hub Genes in Myocardial Infarction Through Bioinformatics Analysis</p>

<p>Screening and Identification of Potential Hub Genes in Myocardial Infarction Through Bioinformatics Analysis</p>

Exogenous IL‐19 attenuates acute ischaemic injury and improves survival in male mice with myocardial infarction

Cyanide Poisoning Compromises Gene Pathways Modulating Cardiac Injury in Vivo

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