High-mobility group box 1 serves as an inflammation driver of cardiovascular disease

Wahid, A. H.; Chen, Wei; Wang, Xuewen; Tang, Xin

doi:10.1016/j.biopha.2021.111555

Cited by 30 publications

(27 citation statements)

References 107 publications

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“…HMGB1 has been linked with angiogenesis, endothelial dysfunction, inflammation, and atherosclerosis through its regulation of toll-like receptor 4 and inflammatory cytokine secretions [ 38 – 43 ]. HMGB1 is expressed in myocardial cells where it selectively binds chromatin and activates innate immune and inflammatory-related genes [ 44 ]. Recently, microRNAs including miR-126 have been shown to confer important regulation of HMGB1 [ 45 – 50 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis

Liu

Wei²,

Wei

et al. 2021

Disease Markers

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Crosstalk between molecular regulators miR-126, hypoxia-inducible factor 1-alpha (HIF-1-α), and high-mobility group box-1 (HMGB1) contributes to the regulation of inflammation and angiogenesis in multiple physiological and pathophysiological settings. Here, we present evidence of an overriding role for miR-126 in the regulation of HMGB1 and its downstream proinflammatory effectors in endothelial cells subjected to hypoxia with concurrent acidosis (H/A). Methods. Primary mouse endothelial cells (PMEC) were exposed to hypoxia or H/A to simulate short or chronic low-flow ischemia, respectively. RT-qPCR quantified mRNA transcripts, and proteins were measured by western blot. ROS were quantified by fluorogenic ELISA and luciferase reporter assays employed to confirm an active miR-126 target in the HMGB1 3 ′ UTR. Results. Enhanced expression of miR-126 in PMECs cultured under neutral hypoxia was suppressed under H/A, whereas the HMGB1 expression increased sequentially under both conditions. Enhanced expression of HMGB1 and downstream inflammation markers was blocked by the premiR-126 overexpression and optimized by antagomiR. Compared with neutral hypoxia, H/A suppressed the HIF-1α expression independently of miR-126. The results show that HMGB1 and downstream effectors are optimally induced by H/A relative to neutral hypoxia via crosstalk between hypoxia signaling, miR-126, and HIF-1α, whereas B-cell lymphoma 2(Bcl2), a HIF-1α, and miR-126 regulated gene expressed optimally under neutral hypoxia. Conclusion. Inflammatory responses of ECs to H/A are dynamically regulated by the combined actions of hypoxia, miR-126, and HIF-1α on the master regulator HMGB1. The findings may be relevant to vascular diseases including atherosclerotic occlusion and interiors of plaque where coexisting hypoxia and acidosis promote inflammation as a defining etiology.

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Section: Introductionmentioning

confidence: 99%

MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis

Liu

Wei²,

Wei

et al. 2021

Disease Markers

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“…Histone methylation only occurs at specific lysine and arginine sites of histone H3 and H4 (36). In histone H3, lysine 4,9,26,27,36,56, and 79 and arginine 2, 8, and 17 can be methylated. By comparison, histone H4 has fewer methylation sites, in which only lysine 5, 12, and 20 and arginine 3 can be methylated (37, 38).…”

Section: Histone Methylation Modificationmentioning

confidence: 99%

“…CVDs might be triggered by multiple processes, such as mitochondrial dysfunction, reactive oxygen species formation, abnormal calcium homeostasis, deleterious phosphorylation signaling, proteostasis imbalance, dysregulated nutrient sensing, cellular senescence, stem cell exhaustion, genomic instability, telomere attrition, and epigenetic alterations (7,8). With the rapid advance in biochemical, molecular, and high-throughput sequencing technologies, the dysregulated expression profiles of the human genome in CVD patients have focused on (9). However, dynamic alterations in the gene expression landscape can contribute to the progression of CVDs (10).…”

Section: Introductionmentioning

confidence: 99%

Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases

Yang

Luan

Yuan

et al. 2021

Front. Cardiovasc. Med.

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The epidemic of cardiovascular diseases (CVDs) is predicted to spread rapidly in advanced countries accompanied by the high prevalence of risk factors. In terms of pathogenesis, the pathophysiology of CVDs is featured by multiple disorders, including vascular inflammation accompanied by simultaneously perturbed pathways, such as cell death and acute/chronic inflammatory reactions. Epigenetic alteration is involved in the regulation of genome stabilization and cellular homeostasis. The association between CVD progression and histone modifications is widely known. Among the histone modifications, histone methylation is a reversible process involved in the development and homeostasis of the cardiovascular system. Abnormal methylation can promote CVD progression. This review discusses histone methylation and the enzymes involved in the cardiovascular system and determine the effects of histone methyltransferases and demethylases on the pathogenesis of CVDs. We will further demonstrate key proteins mediated by histone methylation in blood vessels and review histone methylation-mediated cardiomyocytes and cellular functions and pathways in CVDs. Finally, we will summarize the role of inhibitors of histone methylation and demethylation in CVDs and analyze their therapeutic potential, based on previous studies.

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“…Although several HMGB1 receptors are known, only two receptor systems, RAGE and TLR-4, have been fully elucidated as HMGB1 receptors [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

“…Many receptors, such as CXCR4, proteoglycans, integrins, TIM-3, and CD24, bind to HMGB1 through multi-protein complex formation [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

High Mobility Group Box 1: Biological Functions and Relevance in Oxidative Stress Related Chronic Diseases

Taverna

Tonacci

Ferraro

et al. 2022

Cells

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In the early 1970s, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and named high-mobility group (HMG) proteins. High-mobility group box 1 (HMGB1) is the most studied HMG protein that detects and coordinates cellular stress response. The biological function of HMGB1 depends on its subcellular localization and expression. It plays a critical role in the nucleus and cytoplasm as DNA chaperone, chromosome gatekeeper, autophagy maintainer, and protector from apoptotic cell death. HMGB1 also functions as an extracellular alarmin acting as a damage-associated molecular pattern molecule (DAMP). Recent findings describe HMGB1 as a sophisticated signal of danger, with a pleiotropic function, which is useful as a clinical biomarker for several disorders. HMGB1 has emerged as a mediator in acute and chronic inflammation. Furthermore, HMGB1 targeting can induce beneficial effects on oxidative stress related diseases. This review focus on HMGB1 redox status, localization, mechanisms of release, binding with receptors, and its activities in different oxidative stress-related chronic diseases. Since a growing number of reports show the key role of HMGB1 in socially relevant pathological conditions, to our knowledge, for the first time, here we analyze the scientific literature, evaluating the number of publications focusing on HMGB1 in humans and animal models, per year, from 2006 to 2021 and the number of records published, yearly, per disease and category (studies on humans and animal models).

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High-mobility group box 1 serves as an inflammation driver of cardiovascular disease

Cited by 30 publications

References 107 publications

MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis

MiR-126-HMGB1-HIF-1 Axis Regulates Endothelial Cell Inflammation during Exposure to Hypoxia-Acidosis

Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases

High Mobility Group Box 1: Biological Functions and Relevance in Oxidative Stress Related Chronic Diseases

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