The microRNA in ventricular remodeling: the miR-30 family

Zhang, Xiaonan; Dong, Shaoyang; Jia, Qiujin; Zhang, Ao; Li, Yanyang; Zhu, Yue; Lv, Shichao; Zhang, Junping

doi:10.1042/bsr20190788

Cited by 66 publications

(55 citation statements)

References 111 publications

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“…miR-30 was shown to be cardioprotective in heart failure inhibiting cardiomyocyte autophagy [46]. The miR-30 family is abundant in the heart and to participate in ventricular remodeling through autophagy, inflammatory pathways and apoptotic mechanisms [47]. miR-146a is known to be cardioprotective and to reduce infarct size in in vivo animal models of AMI [48].…”

Section: Discussionmentioning

confidence: 99%

Anti-CD3 Antibody Treatment Reduces Scar Formation in a Rat Model of Myocardial Infarction

Wernly

Paar

Aigner

et al. 2020

Cells

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Introduction: Antibody treatment with anti-thymocyte globulin (ATG) has been shown to be cardioprotective. We aimed to evaluate which single anti-T-cell epitope antibody alters chemokine expression at a level similar to ATG and identified CD3, which is a T-cell co-receptor mediating T-cell activation. Based on these results, the effects of anti-CD3 antibody treatment on angiogenesis and cardioprotection were tested in vitro and in vivo. Methods: Concentrations of IL-8 and MCP-1 in supernatants of human peripheral blood mononuclear cell (PBMC) cultures following distinct antibody treatments were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). In vivo, anti-CD3 antibodies or vehicle were injected intravenously in rats subjected to acute myocardial infarction (AMI). Chemotaxis and angiogenesis were evaluated using tube and migration assays. Intracellular pathways were assessed using Western blot. Extracellular vesicles (EVs) were quantitatively evaluated using fluorescence-activated cell scanning, exoELISA, and nanoparticle tracking analysis. Also, microRNA profiles were determined by next-generation sequencing. Results: Only PBMC stimulation with anti-CD3 antibody led to IL-8 and MCP-1 changes in secretion, similar to ATG. In a rat model of AMI, systemic treatment with an anti-CD3 antibody markedly reduced infarct scar size (27.8% (Inter-quartile range; IQR 16.2-34.9) vs. 12.6% (IQR 8.3-27.2); p < 0.01). The secretomes of anti-CD3 treated PBMC neither induced cardioprotective pathways in cardiomyocytes nor pro-angiogenic mechanisms in human umbilical vein endothelial cell (HUVECs) in vitro. While EVs quantities remained unchanged, PBMC incubation with an anti-CD3 antibody led to alterations in EVs miRNA expression. Conclusion: Treatment with an anti-CD3 antibody led to decreased scar Cells 2020, 9, 295 2 of 19 size in a rat model of AMI. Whereas cardioprotective and pro-angiogenetic pathways were unaltered by anti-CD3 treatment, qualitative changes in the EVs miRNA expression could be observed, which might be causal for the observed cardioprotective phenotype. We provide evidence that EVs are a potential cardioprotective treatment target. Our findings will also provide the basis for a more detailed analysis of putatively relevant miRNA candidates.

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Section: Discussionmentioning

confidence: 99%

Anti-CD3 Antibody Treatment Reduces Scar Formation in a Rat Model of Myocardial Infarction

Wernly

Paar

Aigner

et al. 2020

Cells

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“…It has been reported that the miR-30 family is critical in regulating the expression levels of genes responsible for autophagy, apoptosis, oxidative stress, inflammation, and fibrosis, which are the pathological basis of LVH development [17][18][19] . Indeed, the role of miR-30 family in cardiomyocyte hypertrophy has been reported in cultured cells and animal studies 17,20,21 ; however, the significance of mir-30 family members in a clinical setting has not been evaluated so far.…”

Section: Introductionmentioning

confidence: 99%

“…Mechanistically, the miR-30 family can inhibit autophagy and apoptosis, decrease inflammation, etc., thereby reducing collagen deposition and myocardial fibrosis, and preventing cardiac hypertrophy 19 . We thus detected the correlation between miR-30 family members and the circulating markers for inflammation (hs-CRP) and collagen synthesis (MMP-9).…”

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confidence: 99%

Circulating MicroRNA-30e Predicts Left Ventricular Hypertrophy In Essential Hypertensive Patients

Yang

et al. 2021

RIC

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Background: The biomarker for left ventricular hypertrophy (LVH) in patients with essential hypertension (EH) remains an unmet clinical need. The microRNA-30 (miR-30) family has been associated with LVH in cellular and animal studies, but not in a clinical setting. Objective: The objective of the study was to investigate the clinical significance of circulating levels of miR-30 family as a biomarker for LVH in EH patients. Methods: A total of 239 EH patients and 239 healthy controls were enrolled in this study. Circulating levels of miR-30 family members, namely, miR-30a, miR-30b, miR-30c-1, miR-30c-2, miR-30d, and miR-30e, were evaluated using real-time polymerase chain reaction assays. Results: The circulating miR-30a, miR-30b, and miR-30e were significantly reduced in EH patients in contrast to controls. EH patients with LVH (EH-LVH) had substantially lower circulating miR-30b and miR-30e levels compared to EH patients without LVH (EH-nLVH). Moreover, the expression levels of miR-30b and miR-30e were positively related to LVMI, respectively. Receiver operating curve analysis showed that circulating miR-30e levels distinguished EH patients from controls, and EH-LVH from EH-nLVH patients. Logistic regression analysis identified the circulating miR-30e as a risk factor for LVH in EH patients. Conclusion: Circulating miR-30e level can be used as a biomarker in distinguishing EH-LVH from EH-nLVH. A further prospective study is warranted to validate this finding.

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“…The NLRP3 inflammasome, specifically, is delivered to autolysosomes by autophagy biomarkers LC3 and P62 [13]. Additionally, miRs play an important role in regulating autophagy in many diseases, especially cardiovascular diseases [14][15][16]; however, further studies are needed to investigate the role of miRs in the response to endothelial cell inflammatory injury through end-stage autophagy.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-103 Protects Coronary Artery Endothelial Cells against H₂O₂-Induced Oxidative Stress via BNIP3-Mediated End-Stage Autophagy and Antipyroptosis Pathways

Wang

Song

et al. 2020

Oxidative Medicine and Cellular Longevity

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Endothelial cell damage caused by oxidative stress is widely considered to be a triggering event in atherosclerosis (AS). However, the specific effect elicited by autophagy in endothelial cells undergoing oxidative stress remains controversial, especially during endstage autophagy. The inhibition of end-stage autophagy has been reported to increase cell pyroptosis and contribute to endothelial damage. Several studies have shown that microRNA-103 is involved in end-stage autophagy; however, its specific mechanism of action is not yet characterized. In this study, we addressed the regulatory role of miR-103 in autophagy during oxidative stress of endothelial cells. Hydrogen peroxide (H 2 O 2 ) treatment was used as an in vitro model of oxidative stress. MTS and ROS levels were measured to evaluate cell activity. qRT-PCR was used to detect the expression of miR-103. Autophagy was examined using western blot, immunofluorescence staining, and electron microscopy, while western blot analysis detected pyroptosis-related proteins. Results show that miR-103 expression decreased under oxidative stress. Further, miR-103 repressed transcription of Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3). The oxidative stress caused by H 2 O 2 caused cell damage from 2 hours (P < 0:05) and increased the level of intracellular reactive oxygen species (P < 0:05); at the same time, the damage could be further aggravated by the stimulation of bafA1 (P < 0:05). Under the stimulation of H 2 O 2 , the expression of miR-103 decreased (P < 0:05). However, high expression of miR-103 could reduce the accumulation of LC3II and P62 (P < 0:05) by inhibiting the downstream target gene Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3), thus reducing the occurrence of cell pyroptosis (P < 0:05). This process could be blocked by end-stage autophagy inhibitor bafA1 (P < 0:05), which further indicated that miR-103 affected cell injury by autophagy. On the contrary, the low expression of miR-103 promoted the accumulation of autophagy protein and increased the occurrence of pyroptosis (P < 0:05). In conclusion, inhibition of miR-103 restrained end-stage of autophagy by regulating BNIP3, thus changing the occurrence of cell pyroptosis.

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The microRNA in ventricular remodeling: the miR-30 family

Cited by 66 publications

References 111 publications

Anti-CD3 Antibody Treatment Reduces Scar Formation in a Rat Model of Myocardial Infarction

Anti-CD3 Antibody Treatment Reduces Scar Formation in a Rat Model of Myocardial Infarction

Circulating MicroRNA-30e Predicts Left Ventricular Hypertrophy In Essential Hypertensive Patients

MicroRNA-103 Protects Coronary Artery Endothelial Cells against H₂O₂-Induced Oxidative Stress via BNIP3-Mediated End-Stage Autophagy and Antipyroptosis Pathways

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The microRNA in ventricular remodeling: the miR-30 family

Cited by 66 publications

References 111 publications

Anti-CD3 Antibody Treatment Reduces Scar Formation in a Rat Model of Myocardial Infarction

Anti-CD3 Antibody Treatment Reduces Scar Formation in a Rat Model of Myocardial Infarction

Circulating MicroRNA-30e Predicts Left Ventricular Hypertrophy In Essential Hypertensive Patients

MicroRNA-103 Protects Coronary Artery Endothelial Cells against H2O2-Induced Oxidative Stress via BNIP3-Mediated End-Stage Autophagy and Antipyroptosis Pathways

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Product

Resources

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MicroRNA-103 Protects Coronary Artery Endothelial Cells against H₂O₂-Induced Oxidative Stress via BNIP3-Mediated End-Stage Autophagy and Antipyroptosis Pathways