Low shear stress regulates vascular endothelial cell pyroptosis through miR‐181b‐5p/STAT‐3 axis

Xu, Xiangshan; Yang, Yang; Wang, Guofeng; Yu, Yancun; Han, Shuo; Zheng, Donghan; Zhou, Shuping; Zhao, Yuanyuan; Chen, Yong; Jin, Yinji

doi:10.1002/jcp.29844

Cited by 34 publications

(24 citation statements)

References 31 publications

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“…As an important triggering factor and endogenous regulator of cardiovascular in ammation, pyroptosis not only induces the death of endothelial cells but also leads to enhanced endothelium permeability, promotes the expression of endothelial cell-adhesion molecules, recruits monocytes and promotes their differentiation into macrophages, and aggravates blood vessel damage [42][43][44]. Studies have shown that the pyroptosis regulated by the NLRP3 in ammasome is closely related to the progression of cardiovascular disease [43,45]. It has been shown that GDF11 exerts a cardioprotective effect by inhibiting the cardiomyocyte pyroptosis induced by the NLRP3 in ammasome [15].…”

Section: Discussionmentioning

confidence: 99%

GDF11 Alleviates Neointimal Hyperplasia in Rat Artery Injury Model Via Regulating Endothelial NLRP3-Inflammasome Activation and Rapid Re-Endothelialization

Gao

Liu

et al. 2021

Preprint

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Background Neointimal hyperplasia induced by interventional surgery can lead to progressive obliteration of the vascular lumen, which has become a major factor affecting prognosis. It is commonly accepted that the rate of re-endothelialization is inversely related to neointima formation. Growth differentiation factor 11 (GDF11) is a secreted protein with anti-inflammatory, antioxidant, and anti-aging properties. Recent reports indicate that GDF11 can improve vascular remodeling by maintaining differentiated phenotypes for vascular smooth muscle cells. However, it is not known whether and how GDF11 acts to promote re-endothelialization in vascular injury. The present study was performed to clarify the influence of GDF11 on re-endothelialization after vascular injury. Methods An adult Sprague-Dawley rat model of common-carotid-artery balloon-dilatation injury was surgically established. A recombinant adenovirus carrying GDF11 was delivered into the common carotid artery to overexpress GDF11. Vascular re-endothelialization and neointima formation were carried out on harvested carotid arteries through histomolecular analysis. CCK8 analysis, LDH release and western blotting were performed to investigate the effects of GDF11 on endothelial NLRP3-inflammasome activation and relevant signaling pathways in vitro. Results GDF11 significantly enhanced re-endothelialization and reduced neointima formation in rats with balloon-dilatation injury by suppressing the activation of the NLRP3 inflammasome. Endoplasmic-reticulum stress (ER stress) inhibitor, 4PBA administration attenuated endothelial NLRP3-inflammasome activation induced by Lysophosphatidylcholine. Besides, up-regulation of LOX1 expression involved elevated endoplasmic-reticulum stress, and could result in endothelial NLRP3-inflammasome activation. Moreover, GDF11 significantly inhibited NLRP3-inflammasome-mediated endothelial cell pyroptosis through the negative regulation of LOX-1-dependent ER stress. Conclusions We conclude that GDF11 improves re-endothelialization and can attenuate vascular remodeling by reducing endothelial NLRP3-inflammasome activation. These findings shed light on new treatment strategies to promote re-endothelialization based on GDF11 as a future target.

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Section: Discussionmentioning

confidence: 99%

GDF11 Alleviates Neointimal Hyperplasia in Rat Artery Injury Model Via Regulating Endothelial NLRP3-Inflammasome Activation and Rapid Re-Endothelialization

Gao

Liu

et al. 2021

Preprint

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“…Low shear stress plays a critical role in the development of atherosclerosis. Regulation of miR181b‐5p and transcriptional activation factor 3 (STAT‐3) expression induces NLRP3‐dependent pyroptosis (X. Xu et al, 2020).…”

Section: Role Of Pyroptosis In Atherosclerosismentioning

confidence: 99%

Role of pyroptosis in atherosclerosis and its therapeutic implications

Nie

Wang

et al. 2021

Journal Cellular Physiology

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Atherosclerosis is a significant cardiovascular burden and a leading cause of death worldwide, recognized as a chronic sterile inflammatory disease. Pyroptosis is a novel proinflammatory regulated cell death, characterized by cell swelling, plasma membrane bubbling, and robust release of proinflammatory cytokines (such as interleukin IL‐1β and IL‐18). Mounting studies have addressed the crucial contribution of pyroptosis to atherosclerosis and clarified the candidate therapeutic agents targeting pyroptosis for atherosclerosis. Herein, we review the initial characterization of pyroptosis, the detailed mechanisms of pyroptosis, current evidence about pyroptosis and atherosclerosis, and potential therapeutic strategies that target pyroptosis in the development of atherosclerosis.

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“…77 In addition to ox-LDL, shear stress changes caused by abnormal blood flow are an important factor in atherosclerosis and low fluid shear stress is conducive to the occurrence of atherosclerosis and plate growth. Xu et al 78 reported that low shear stress can downregulate mechanosensitive miR-181-5p expression and induce pyroptosis in HUVECs. Moreover, miR-181-5p mimic transfection can suppress signal transduction and transcriptional activation factor 3 (STAT3) gene expression by directly binding to its 3 0 UTR, resulting in reduced NLRP3 transcription through lysine deacetylation and amelioration of NLRP3 inflammasome-dependent pyroptosis.…”

Section: Atherosclerosismentioning

confidence: 99%

“…Moreover, miR-181-5p mimic transfection can suppress signal transduction and transcriptional activation factor 3 (STAT3) gene expression by directly binding to its 3 0 UTR, resulting in reduced NLRP3 transcription through lysine deacetylation and amelioration of NLRP3 inflammasome-dependent pyroptosis. 78 lncRNAs Intragastric administration of melatonin decreases expression of the pyroptosis-associated genes NLRP3, ASC, cleaved caspase-1, NF-kB/GSDMD, and GSDMD N-termini and markedly reduces atherosclerotic plaques in high-fat diet-treated ApoE À/À mouse aortas. 79 Mechanistically, melatonin downregulates lncRNA MEG3, high expression of which enhances pyroptosis in HAECs.…”

Section: Atherosclerosismentioning

confidence: 99%

Regulation of pyroptosis in cardiovascular pathologies: Role of noncoding RNAs

Gao

Chen

Wei

et al. 2021

Molecular Therapy - Nucleic Acids

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Cardiovascular disease (CVD) is one of the most important diseases endangering human life. The pathogenesis of CVDs is complex. Pyroptosis, which differs from traditional apoptosis and necrosis, is characterized by cell swelling until membrane rupture, resulting in the release of cell contents and activation of a strong inflammatory response. Recent studies have revealed that inflammation and pyroptosis play important roles in the progression of CVDs. Noncoding RNAs (ncRNAs) are considered promising biomarkers and potential therapeutic targets for the diagnosis and treatment of various diseases, including CVDs. Growing evidence has revealed that ncRNAs can mediate the transcriptional or posttranscriptional regulation of pyroptosis-related genes by participating in the pyroptosis regulatory network. The role and molecular mechanism of pyroptosis-regulating ncRNAs in cardiovascular pathologies are attracting increasing attention. Here, we summarize research progress on pyroptosis and the role of ncRNAs, particularly microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), in the regulation of pyroptosis in CVD pathologies. Identifying these disease-related ncRNAs is important for understanding the pathogenesis of CVDs and providing new targets and ideas for their prevention and treatment.Noncoding RNAs (ncRNAs) account for up to 98%-99% of the human genome and participate in regulating the expression of protein-coding genes. 10,11 The interaction between ncRNAs and protein-coding genes forms a highly complex RNA regulatory network. Abnormalities in ncRNAs are closely related to numerous diseases. Recent efforts to identify the molecular mechanisms underlying the pathogenesis of CVDs have revealed a significant regulatory role of ncRNAs in the occurrence and development of major CVDs, such as myocardial infarction, coronary heart disease, atrial fibrillation, atherosclerosis, cardiomyopathy, and heart failure. [12][13][14] The main classes of ncRNAs are microRNAs (miRNAs), long ncRNAs

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Low shear stress regulates vascular endothelial cell pyroptosis through miR‐181b‐5p/STAT‐3 axis

Cited by 34 publications

References 31 publications

GDF11 Alleviates Neointimal Hyperplasia in Rat Artery Injury Model Via Regulating Endothelial NLRP3-Inflammasome Activation and Rapid Re-Endothelialization

GDF11 Alleviates Neointimal Hyperplasia in Rat Artery Injury Model Via Regulating Endothelial NLRP3-Inflammasome Activation and Rapid Re-Endothelialization

Role of pyroptosis in atherosclerosis and its therapeutic implications

Regulation of pyroptosis in cardiovascular pathologies: Role of noncoding RNAs

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