Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, microRNAs (miRNAs) have been shown to involve in the process of heart failure. This study aims to investigate the functional role of miR-147b in rat H9c2 cardiomyocytes and explore the underlying molecular mechanisms. Cell viability of H9c2 cells was detected by MTT assay. Cell apoptosis was detected by flow cytometry. Expression of miR-147b and KLF13 mRNA was detected by quantitative real-time PCR. The relationship between miR-147b and KLF13 was verified by dual-luciferase reporter assay. Protein levels were detected by western blot analysis. It was found that H2O2 inhibited cell viability and promoted cell apoptosis of H9c2 cells in a concentration-dependent manner. MiR-147b overexpression suppressed cell viability and increased apoptosis in H9c2 cells, while knock-down of miR-147b increased cell viability and reduced apoptosis in H2O2-treated H9c2 cells. Luciferase reporter assay and in vitro functional assay showed that KLF13 was a downstream target of miR-147b, and KLF13 knock-down suppressed cell viability and induced apoptosis in H9c2 cells. Enforced expression of KLF13 restored the effects of miR-147b overexpression on cell viability and apoptosis in H9c2 cells. MiR-147b modulated the expression levels of apoptosis-related proteins, and the effects of miR-147b overexpression on apoptosis-related proteins levels were prevented by enforced expression of KLF13 in H9c2 cells. The in vivo experiments showed that miR-147b was up-regulated, and KLF13 was down-regulated in the myocardial tissues from rats with chronic heart failure. Collectively, miR-147b inhibits viability and promotes cell apoptosis by targeting KLF13 in H9c2 cells, which may be associated with the pathogenesis of heart failure.
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PMID:MiR-147b inhibits cell viability and promotes apoptosis of rat H9c2 cardiomyocytes via down-regulating KLF13 expression. 2937 79

Oxidative stress contributes to myocardial ischemia-reperfusion injury, which causes cardiomyocyte death and precipitate life-threatening heart failure. Propofol has been proposed to protect cells or tissues against oxidative stress. However, the mechanisms underlying its beneficial effects are not fully elucidated. In the present study, we employed an in vitro oxidative injury model, in which rat cardiac H9c2 cells were treated with H2O2, and investigated roles of propofol against oxidative stress. Propofol treatment reduced H2O2-induced apoptotic cell death. While H2O2 induced expression of the antioxidant enzyme HO-1, propofol further increased HO-1 mRNA and protein levels. Propofol also promoted nuclear localization of Nrf2 in the presence of H2O2. Knockdown of Nrf2 using siRNA suppressed propofol-inducible Nrf2 and expression of Nrf2-downstream antioxidant enzyme. Knockdown of Nrf2 suppressed the propofol-induced cytoprotection. In addition, Nrf2 overexpression induced nuclear localization of Nrf2 and HO-1 expression. These results suggest that propofol exerts antioxidative effects by inducing nuclear localization of Nrf2 and expression of its downstream enzyme in cardiac cells. Finally, we examined the effect of propofol on cardiomyocytes using myocardial ischemia-reperfusion injury models. The expression level of Nrf2 protein was increased at 15 min after reperfusion in the ischemia-reperfusion and propofol group compared with ischemia-reperfusion group in penumbra region. These results suggest that propofol protects cells or tissues from oxidative stress via Nrf2/HO-1 cascade.
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PMID:Propofol induces nuclear localization of Nrf2 under conditions of oxidative stress in cardiac H9c2 cells. 2968 82

The main function of NADPH oxidases is to catalyse the formation of reactive oxygen species (ROS). NADPH oxidase 4 (NOX4) is expressed at high levels in kidney tubular cells, and at lower levels in endothelial cells, cardiomyocytes and other cell types under physiological conditions. NOX4 is constitutively active producing hydrogen peroxide (H2O2) as the prevalent ROS detected, whereas other NOX isoforms present in the renal and cardiovascular systems (i.e. NOX1, NOX2 and NOX5) generate superoxide radical anions as main products. Pharmacological inhibition of NOX4 has received enormous attention for its potential therapeutic benefit in fibrotic disease and nephropathologies. Ongoing clinical trials are testing this approach in humans. Diabetes elevates NOX4 expression in podocytes and mesangial cells, which was shown to damage glomeruli leading to podocyte loss, mesangial cell hypertrophy and matrix accumulation. Consequently, NOX4 represents an interesting therapeutic target in diabetic nephropathy. On the contrary, experiments using NOX4-deficient mice have shown that NOX4 is cytoprotective in tubular cells, cardiomyocytes, endothelial cells and vascular smooth muscle cells, and has a metabolism-regulating role when these cells are subjected to injury. Mice with systemic NOX4 deletion are more susceptible to acute and chronic tubular injury, heart failure and atherosclerosis. Overall, the current literature suggests a detrimental role of increased NOX4 expression in mesangial cells and podocytes during diabetic nephropathy, but a cytoprotective role of this enzyme in other cellular types where it is expressed endogenously. We review here the recent evidence on the role of NOX4 in the kidneys and cardiovascular system. With the emergence of pharmacological NOX4 inhibitors in clinical trials, caution should be taken in identifying potential side effects in patients prone to acute kidney injury and cardiovascular disease.
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PMID:Potential benefits and harms of NADPH oxidase type 4 in the kidneys and cardiovascular system. 2993 36

Recent studies have revealed the important role of long noncoding RNAs (lncRNAs) in heart development and pathogenesis. This study was aimed to investigate the role of NEAT1 in hypoxia-induced cardiac injury and explore its possible molecular mechanism. Real-time PCR (RT-PCR) was used to determine the relative RNA expression of NEAT1 and its potential target microRNA, miR-129-5p, in the plasma of patients with acute myocardial infarction, heart failure, and angina, as well as in H2O2-treated H9c2 cells. The role of NEAT1 overexpression or inhibition in H9c2 cell migration and proliferation was assessed by transwell assay and Edu staining, respectively. Collagen deposition and apoptosis were evaluated by Western blot detection of collagen and apoptotic proteins, including Capase3, Bax, and Bcl2. We showed that H2O2 treatment significantly decreased H9c2 cell migration and proliferation while increasing H9c2 cell apoptosis. Inhibition of NEAT1 attenuated the cell apoptosis and alleviated proliferation inhibition induced by hypoxia. Bioinformatics analysis showed that miR-129-5p was the direct target of NEAT1, which was confirmed by luciferase assay. NEAT1 upregulation aggravated apoptosis by downregulating miR-129-5p. In conclusion, we uncovered a novel NEAT1-miR-129 axis and its implication in H2O2-induced heart failure.
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PMID:Long Noncoding RNA NEAT1 Promotes Myocardiocyte Apoptosis and Suppresses Proliferation Through Regulation of miR-129-5p. 3181 67

Matrine is a main active constituent of Chinese herb Sophora flavescens Ait (Kushen), which has shown various pharmacological effects, and has been reported to exhibit protective effects in heart failure. In the present study, the underlying mechanism of matrine was explored in H2O2-induced H9c2 cell line. It was confirmed that matrine could alleviate H2O2-induced injury in H9c2 cells. And the down-regulation of long non-coding RNA HOTAIR induced by H2O2 could be reversed by treating with matrine. Moreover, overexpression of HOTAIR promoted cell viability and superoxide dismutase (SOD) level, but inhibited cell apoptosis and lactate dehydrogenase (LDH) level. We found that miR-106b-5p was a target of HOTAIR and negatively regulated by HOTAIR. Moreover, up-regulation of miR-106b-5p restored the effects of HOTAIR overexpression on cell viability, apoptosis, and the levels of LDH and SOD. In addition, matrine protected H9c2 cells from H2O2-induced injury through HOTAIR/miR-106b-5p axis. Furthermore, we discovered that matrine exerted protective effects on H2O2-induced H9c2 cells through activating STAT3 and AKT pathway. In brief, matrine modulated H2O2-induced myocardial oxidative stress repair through HOTAIR/miR-106b-5p axis via AKT and STAT3 signaling pathway. Our study may provide a therapeutic target for the therapy of oxidative stress heart diseases.
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PMID:Matrine regulates H2O2-induced oxidative stress through long non-coding RNA HOTAIR/miR-106b-5p axis via AKT and STAT3 pathways. 3239 44

Oxidative stress significantly contributes to heart disease, and thus might be a promising target for ameliorating heart failure. Mounting evidence suggests that selenium has chemotherapeutic potential for treating heart disease due to its regulation of selenoproteins, which play antioxidant regulatory roles. Oxidative stress-induced cardiomyocyte cell cycle arrest contributes to the loss of cardiomyocytes during heart failure. The protective effects and mechanism of selenium against oxidative stress-induced cell cycle arrest in cardiomyocytes warrant further study. H9c2 rat cardiomyoblast cells were treated with hydrogen peroxide in the presence or absence of selenium supplementation. Na2SeO3 pretreatment alleviated H2O2-induced oxidative stress, increased thioredoxin reductase (TXNRD) activity and glutathione peroxidase (GPx) activity and counteracted the H2O2-induced cell cycle arrest at the S phase. These effects were accompanied by attenuation of the H2O2-induced strengthening of the G2/M-phase inhibitory system, including increased mRNA and protein levels of cyclin-dependent kinase 1 (CDK1) and decreased p21 mRNA levels. Notably, Na2SeO3 pretreatment activated the PI3K/AKT signaling pathway, and inhibition of PI3K counteracted the protective effects of selenium on H2O2-induced cell cycle arrest. We corroborated our findings in vivo by inducing oxidative stress in pig heart by feeding a selenium deficient diet, which decreased the TXNRD activity, inactivated PI3K/AKT signaling and strengthened the G2/M-phase inhibitory system. We concluded that the cardioprotective effects of selenium supplementation against oxidative stress-induced cell cycle arrest in cardiomyocytes might be mediated by the selenoprotein-associated (GPx and TXNRD) antioxidant capacity, thereby activating redox status-associated PI3K/AKT pathways, which promote cell cycle progression by targeting the G2/M phase inhibitory system. This study provides new insight into the underlying mechanisms of cardioprotection effects of selenium at the cellular level.
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PMID:Selenium supplementation protects against oxidative stress-induced cardiomyocyte cell cycle arrest through activation of PI3K/AKT. 3323 45


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