MiR-30b Is Involved in the Homocysteine-Induced Apoptosis in Human Coronary Artery Endothelial Cells by Regulating the Expression of Caspase 3

Li, Feng; Chen, Qi; Song, Xiaowei; Zhou, Lei; Zhang, Jianliang

doi:10.3390/ijms160817682

Cited by 26 publications

(17 citation statements)

References 32 publications

(35 reference statements)

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“…Most of these pathways are also known to be related to both micro and macrovascular complications during type 2 diabetes [ 92 , 93 ]. From the analysis, we found various endothelial cell specific genes such as nitric oxide synthase (NOS3) and endothelin (EDN1) as well as other genes related to vascular dysfunction such as endothelial permeability (ERG, RHOA, ROCK) [ 94 , 95 , 96 , 97 , 98 ], inflammation (CCL5, TLR4, NFKB1 and IL1B) [ 99 , 100 , 101 ] and apoptosis (BNIP3, DNM1L, BCL-2, MCL-1 and CASP3) [ 102 , 103 , 104 , 105 , 106 ] to be dysregulated ( Table S4 ). These data clearly indicate that the hyperglycemia can result in endothelial dysfunction and the event can be analyzed from the mRNA data of the blood.…”

Section: Resultsmentioning

confidence: 99%

MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

Maskomani

Tan

Karolina

et al. 2016

IJMS

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Hyperglycemia is closely associated with prediabetes and Type 2 Diabetes Mellitus. Hyperglycemia increases the risk of vascular complications such as diabetic retinopathy, diabetic nephropathy, peripheral vascular disease and cerebro/cardiovascular diseases. Under hyperglycemic conditions, the endothelial cells become dysfunctional. In this study, we investigated the miRNA expression changes in human umbilical vein endothelial cells exposed to different glucose concentrations (5, 10, 25 and 40 mM glucose) and at various time intervals (6, 12, 24 and 48 h). miRNA microarray analyses showed that there is a correlation between hyperglycemia induced endothelial dysfunction and miRNA expression. In silico pathways analyses on the altered miRNA expression showed that the majority of the affected biological pathways appeared to be associated to endothelial cell dysfunction and apoptosis. We found the expression of ten miRNAs (miR-26a-5p, -26b-5p, 29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -140-5p, -192-5p, -221-3p and -320a) to increase gradually with increasing concentration of glucose. These miRNAs were also found to be involved in endothelial dysfunction. At least seven of them, miR-29b-3p, -29c-3p, -125b-1-3p, -130b-3p, -221-3p, -320a and -192-5p, can be correlated to endothelial cell apoptosis.

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Section: Resultsmentioning

confidence: 99%

MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

Maskomani

Tan

Karolina

et al. 2016

IJMS

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“…Moreover, miRNA profiling of human endometrium reveals cyclic changes in miR30b expression through the different physiological phases [43], and sex differences of miR30b levels were also observed in brains of female schizophrenic patients compared to males [44], suggesting the effect of physiological concentrations of estrogen on miR-30b regulation. In endothelial cells, miR-30 has also been implicated in angiogenesis processes [45], antiinflammatory effects by decreasing angiopoietin 2-induced VCAM1 expression [46] and apoptosis inhibition of human coronary artery endothelial cells [47]. In this regard, it is noteworthy that E2 has also pro-angiogenic, anti-inflammatory and anti-apoptotic properties in response to vascular injury [4].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

Vidal‐Gómez

Pérez‐Cremades

Mompeón

et al. 2018

Cell Physiol Biochem

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Background/Aims: Estrogen signalling plays an important role in vascular biology as it modulates vasoactive and metabolic pathways in endothelial cells. Growing evidence has also established microRNA (miRNA) as key regulators of endothelial function. Nonetheless, the role of estrogen regulation on miRNA profile in endothelial cells is poorly understood. In this study, we aimed to determine how estrogen modulates miRNA profile in human endothelial cells and to explore the role of the different estrogen receptors (ERα, ERβ and GPER) in the regulation of miRNA expression by estrogen. Methods: We used miRNA microarrays to determine global miRNA expression in human umbilical vein endothelial cells (HUVEC) exposed to a physiological concentration of estradiol (E2; 1 nmol/L) for 24 hours. miRNAgene interactions were computationally predicted using Ingenuity Pathway Analysis and changes in miRNA levels were validated by qRT-PCR. Role of ER in the E2-induced miRNA was additionally confirmed by using specific ER agonists and antagonists. Results: miRNA array revealed that expression of 114 miRNA were significantly modified after E2 exposition. Further biological pathway analysis revealed cell death and survival, lipid metabolism, reproductive system function, as the top functions regulated by E2. We validated changes in the most significantly increased (miR-30b-5p, miR-487a-5p, miR-4710, miR-501-3p) and decreased (miR-378h and miR-1244) miRNA and the role of ER in these E2-induced miRNA was determined. Results showed that both classical, ERα and ERβ, and membrane-bound ER, GPER, differentially regulated specific miRNA. In silico analysis of validated miRNA promoters identified specific ER binding sites. Conclusion: Our findings identify differentially expressed miRNA pathways linked to E2 in human endothelial cells through ER, and provide new insights by which estrogen can modulate endothelial function.

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“…proliferation and apoptosis of coronary artery endothelial cells via integrin subunit α 4, phospholipase γ 1 (48), caspase 3 (49) and Bcl-2 (50). Furthermore, myocardial miR-30b serves anti-apoptotic and protective roles during the pathological process of heart ischemia reperfusion (51,52).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑30b protects myocardial cell function in patients with acute myocardial ischemia by targeting plasminogen activator inhibitor‑1

Chen

2018

Exp Ther Med

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The aim of the present study was to determine the expression of plasminogen activator inhibitor-1 (PAI-1) and microRNA (miR)-30b in the blood of patients with acute myocardial ischemia (AMI) and in the blood and myocardial tissue of mice with AMI. In addition, the present study aimed to identify the mechanism of action of miR-30b in AMI. A total of 36 patients with AMI were included in the present study and 28 healthy subjects were included as a control. Peripheral blood was collected from all subjects. For animal experiments, mice in the AMI group received an intraperitoneal injection of pituitrin (20 U/kg), whereas mice in the negative control group received an intraperitoneal injection of the same volume of saline. Blood and myocardial tissue was collected from all mice for analysis. Reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of PAI-1 mRNA and miR-30b in the serum and myocardial tissue. An enzyme-linked immunosorbent assay was performed to measure the expression of PAI-1 protein in the serum of humans and mice, whereas western blotting was performed to determine the expression of PAI-1 protein in mouse myocardial tissue. Catalase, glutathione peroxidase and superoxide dismutase activity was measured using an automatic biochemical analyzer. A dual luciferase assay was performed to identify the interactions between PAI-1 mRNA and miR-30b. The results indicated that patients with AMI have higher PAI-1 levels and lower miR-30b expression in the peripheral blood compared with healthy subjects. AMI damaged the myocardium tissue of mice and reduced catalase, glutathione peroxidase and superoxide dismutase activity. Mice that have undergone AMI exhibit increased PAI-1 levels but decreased miR-30b expression in the peripheral blood and myocardial tissues. It was also demonstrated that miR-30b is able to bind to the 3'-untranslated region of PAI-1 mRNA to regulate its expression. The present study demonstrates that patients with AMI exhibit decreased miR-30b expression and elevated PAI-1 expression in the peripheral blood. miR-30b may therefore inhibit the damage to myocardial cells that occurs following AMI and protect myocardial cell function by targeting PAI-1 expression.

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MiR-30b Is Involved in the Homocysteine-Induced Apoptosis in Human Coronary Artery Endothelial Cells by Regulating the Expression of Caspase 3

Cited by 26 publications

References 32 publications

MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

MicroRNAs in Hyperglycemia Induced Endothelial Cell Dysfunction

MicroRNA as Crucial Regulators of Gene Expression in Estradiol-Treated Human Endothelial Cells

MicroRNA‑30b protects myocardial cell function in patients with acute myocardial ischemia by targeting plasminogen activator inhibitor‑1

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