The protective effects of GLP-1 receptor agonist lixisenatide on oxygen-glucose deprivation/reperfusion (OGD/R)-induced deregulation of endothelial tube formation

Xiao, Mochao; Lu, Daifeng; Tian, Jiali; Yu, Yang; Zhang, Qin; Zhang, Lili; Chang, Dong

doi:10.1039/c9ra09959j

Cited by 7 publications

(8 citation statements)

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“…The combination of LAD ligation and the OGD model is commonly used in vivo and in vitro studies of AMI (Xiao et al, 2020;Wang et al, 2021;Zhang et al, 2021;. As early as 2000, researchers used the OGD model to simulate oxidative stress in myocardial cells under ischemic and hypoxic conditions (Persky et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic and Genetic Mechanisms Underlying Cardiovascular Diseases and Neurodevelopmental Disorders

2024

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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Section: Discussionmentioning

confidence: 99%

Epigenetic and Genetic Mechanisms Underlying Cardiovascular Diseases and Neurodevelopmental Disorders

2024

Frontiers Research Topics

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“…Acute myocardial infarction (AMI) is a complication of atherosclerosis that takes place in the coronary arteries. [17] It causes severe damage to the coronary microcirculation, resulting in vascular disintegration and capillary thinning in the infarct zone. Cardiac endothelial cells are estimated to be almost triple the number of cardiomyocytes [17,18] .…”

Section: Discussionmentioning

confidence: 99%

“…[17] It causes severe damage to the coronary microcirculation, resulting in vascular disintegration and capillary thinning in the infarct zone. Cardiac endothelial cells are estimated to be almost triple the number of cardiomyocytes [17,18] . Endothelial dysfunction is involved from the initial stage of atherosclerosis to the late stage of cardiovascular complications.…”

Section: Discussionmentioning

confidence: 99%

“…[24] Furthermore, animal studies also support the notion that post-AMI endogenous angiogenic responses can be boosted to reduce scarring and adverse left ventricular remodeling. [25] The combination of LAD ligation and the OGD model is commonly used in vivo and in vitro studies of AMI [17,24,[26][27][28] . As early as 2000, researchers used the OGD model to simulate oxidative stress in myocardial cells under ischemic and hypoxic conditions.…”

Section: Discussionmentioning

confidence: 99%

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Role of DNA Methylation in Ischemic-Hypoxic Endothelial Cells and its Clinical Implications in AMI Patients

Tang,

Wang,

Wang

et al. 2023

Preprint

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The obstructed coronary artery undergoes a series of pathological changes due to ischemia and hypoxic shocks during acute myocardial infarction (AMI). However, the altered DNA methylation levels in endothelial cells under these conditions and their implication for the etiopathology of AMI have not been investigated in detail. This study aimed to explore the relationship between DNA methylation and pathologically altered gene expression profile in human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation (OGD), and its clinical implications in AMI Patients. The Illumina Infinium MethylationEPIC BeadChip assay was used to explore the genome-wide DNA methylation profile using the Novaseq6000 platform for mRNA sequencing in 3 pairs of HUVEC-OGD and control samples. GO and KEGG pathway enrichment analyses, as well as correlation, causal inference test (CIT), and protein-protein interaction (PPI) analyses identified 22 hub genes that were validated by MethylTarget sequencing as well as qRT-PCR. ELISA was used to detect four target molecules associated with the progression of AMI. A total of 2524 differentially expressed genes (DEGs) and 22148 differentially methylated positions corresponding to 6642 differentially methylated genes were screened (|Δβ|>0.1 and detection p<0.05). After GO, KEGG, correlation, CIT, and PPI analyses, 441 genes were filtered. qRT-PCR confirmed the overexpression of VEGFA, CCL2, THBS1, SQSTM1, BCL2L11, and TIMP3 genes, and downregulation of MYC, CD44, BDNF, GNAQ, RUNX1, ETS1, NGFR, MME, SEMA6A, GNAI1, IFIT1, and MEIS1. DNA fragments BDNF_1_ (r=0.931, p<0.0001) and SQSTM1_2_NEW (r=0.758, p=0.0043) were positively correlated with the expressions of corresponding genes, and MYC_1_ (r=-0.8245, p=0.001) was negatively correlated. Furthermore, ELISA confirmed TNFSF10 and BDNF were elevated in the peripheral blood of AMI patients (p=0.0284 and p=0.0142, respectively). Combined sequencing from in-vitro cellular assays with clinical samples, focusing on the importance of endothelial cells in AMI, our study identified promising OGD-specific genes, which provided a solid basis for screening fundamental diagnostic and prognostic biomarkers of coronary endothelial cell injury of AMI. Moreover, it furnished the first evidence that during ischemia and hypoxia, the expression of BNDF was regulated by DNA methylation in endothelial cells and elevated in peripheral blood.

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“…Also, liraglutide functions as a catalyst to promote endothelial cell migration and proliferation, directly affecting vascular endothelial repair and revascularization ( Yue et al, 2019 ). In addition, eNOS is not only expressed in endothelial cells but also in cardiomyocytes ( Xiao et al, 2020 ). Regulation of cardiac NO synthesis has been suggested as a common pathway to explain the benefits of multiple effective therapies for ASCVD ( Aung et al, 2019 ).…”

Section: Molecular Mechanism Of Anti-as By Glp-1rasmentioning

confidence: 99%

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

Wang,

Ding,

Cheng

et al. 2024

Front. Pharmacol.

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Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of cardiovascular mortality and is increasingly prevalent in our population. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can safely and effectively lower glucose levels while concurrently managing the full spectrum of ASCVD risk factors and improving patients’ long-term prognosis. Several cardiovascular outcome trials (CVOTs) have been carried out to further investigate the cardiovascular benefits of GLP-1RAs. Analyzing data from CVOTs can provide insights into the pathophysiologic mechanisms by which GLP-1RAs are linked to ASCVD and define the use of GLP-1RAs in clinical practice. Here, we discussed various mechanisms hypothesized in previous animal and preclinical human studies, including blockade of the production of adhesion molecules and inflammatory factors, induction of endothelial cells’ synthesis of nitric oxide, protection of mitochondrial function and restriction of oxidative stress, suppression of NOD-like receptor thermal protein domain associated protein three inflammasome, reduction of foam cell formation and macrophage inflammation, and amelioration of vascular smooth muscle cell dysfunction, to help explain the cardiovascular benefits of GLP-1RAs in CVOTs. This paper provides an overview of the clinical research, molecular processes, and possible therapeutic applications of GLP-1RAs in ASCVD, while also addressing current limitations in the literature and suggesting future research directions.

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The protective effects of GLP-1 receptor agonist lixisenatide on oxygen-glucose deprivation/reperfusion (OGD/R)-induced deregulation of endothelial tube formation

Abstract: Acute myocardial infarction (AMI) is a complication of atherosclerosis that takes place in coronary arteries.

Cited by 7 publications

References 29 publications

Epigenetic and Genetic Mechanisms Underlying Cardiovascular Diseases and Neurodevelopmental Disorders

Epigenetic and Genetic Mechanisms Underlying Cardiovascular Diseases and Neurodevelopmental Disorders

Role of DNA Methylation in Ischemic-Hypoxic Endothelial Cells and its Clinical Implications in AMI Patients

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

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