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1.
Am J Transl Res ; 14(9): 6175-6186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36247255

RESUMO

OBJECTIVES: Long non-coding RNAs (lncRNAs) are known to be involved in heart development and function. In this study, we aimed to explore the effect of the lncRNA FGD5 antisense RNA 1 (FGD5-AS1) on acute myocardial infarction (AMI) by targeting miR-223-3p. METHODS: An AMI model was established both in vivo and in vitro. The levels of FGD5-AS1, miR-223-3p and inflammatory factors were detected by real-time quantitative reverse transcription PCR. Cardiomyocyte apoptosis was assessed using TdT-mediated dUTP nick-end labeling assay. The protein levels of cleaved caspase-3, Bcl-2 and Bax were examined using Western blot. Cardiac function was evaluated using hemodynamic analysis and hematoxylin-eosin and Masson's trichrome staining. In addition, an underlying competitive endogenous RNA mechanism was revealed by bioinformatics analysis, dual-luciferase reporter assay and rescue experiments. RESULTS: We found decreased expression of FGD5-AS1 in AMI. Furthermore, FGD5-AS1 expression significantly decreased the infarct size, improved cardiac performance and attenuated cardiac fibrosis by reducing myocardial apoptosis and inflammation. miR-223-3p was a direct target of FGD5-AS1. Moreover, miRNA-223-3p directly downregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes. Further experiments demonstrated that FGD5-AS1 modulated Akt activity to reduce myocardial injury through miR-223-3p. CONCLUSION: The FGD5-AS1/miR-223-3p/Akt pathway is involved in AMI, suggesting that FGD5-AS1 may act as a potential biomarker and therapeutic target for AMI.

2.
J Drug Target ; 30(8): 858-872, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35400245

RESUMO

To explore the mechanisms underlying the specific inhibitor targeting SGLT-2 empagliflozin in alleviating myocardial ischaemia-reperfusion (I/R) injury. A mouse model of I/R injury and H2O2-induced H9C2 cell model were established. The expressions of Bcl-2, Bax, LC3, Beclin1, GRP78, CHOP, PERK, ATF4, ATF6, IREα and P62 were examined by western blot, immunofluorescence or immunohistochemistry staining, respectively. The cardiac function was measured by echocardiography, TCC staining, lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity. Cell apoptosis was analysed by TUNEL, Annexin V/propidium iodide (PI) staining and caspase 3 and 9 activities. CCK-8 assay was used for analysing cell viability. PBA, TUDC and 3-MA were utilised for blocking ER stress and autophagy, respectively. Empagliflozin suppressed myocardial I/R injury in vivo and H2O2-induced cardiomyocyte apoptosis in vitro. Blockade of ER stress and autophagy inhibited H2O2-induced cardiomyocyte apoptosis. ER stress activated autophagy through the PERK signalling in H2O2-treated H9C2 cells. Empagliflozin suppressed ER stress-induced autophagy by inhibiting the PERK/ATF4/Beclin1 signalling. H2O2 and I/R-induced cardiomyocyte apoptosis was restrained by empagliflozin through inhibition of ER stress-induced autophagy. Empagliflozin suppressed ER stress-induced autophagy via suppressing the PERK/ATF4/Beclin1 signalling, thus alleviating myocardial I/R injury and cardiomyocyte apoptosis.


Assuntos
Traumatismo por Reperfusão Miocárdica , Animais , Apoptose , Autofagia , Proteína Beclina-1 , Compostos Benzidrílicos , Estresse do Retículo Endoplasmático , Glucosídeos , Peróxido de Hidrogênio/metabolismo , Camundongos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos
3.
PLoS One ; 15(11): e0242606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33211757

RESUMO

Gestational zinc deficiency is a cause of congenital heart disease in the fetus, and sentrin/small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) as deSUMOylation enzymes play a crucial role in the development of cardiac structures. However, current studies of the regulation and function of SENP in zinc-deficient status during heart development remain limited. In this study, SUMO1 modification was found to gradually decrease during heart development, and the level of SENP5 exhibited a similar trend to SUMO1 conjugation. In addition, zinc deficiency resulted in cardiac dysplasia, increased cell apoptosis, decreased cell viability, and differentiation inhibition of hiPSC-CMs. In order to investigate the function of SENP5 in zinc deficiency, hiPSC-CMs were transfected with SENP5 small interfering RNA. The negative effects of zinc lacking conditions were reversed with depletion of SENP5. It was confirmed that zinc deficiency induced abnormal differentiation of hiPSCs and increased apoptosis of hiPSC-CMs by promoting SENP5 overexpression, which led to cardiac dysplasia. Thus, it was concluded that SENP5 regulates the SUMO1 deconjugation during heart development and zinc deficiency may reduce conjugated SUMO by promoting SENP5 overexpression, which induces abnormal development of the myocardium.


Assuntos
Diferenciação Celular , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica , Células-Tronco Pluripotentes Induzidas/metabolismo , Miocárdio/enzimologia , Miócitos Cardíacos/enzimologia , Peptídeo Hidrolases/biossíntese , Zinco/deficiência , Animais , Linhagem Celular , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Masculino , Camundongos , Miocárdio/patologia , Miócitos Cardíacos/patologia , Proteína SUMO-1/metabolismo
4.
J Int Med Res ; 48(10): 300060520966500, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33115315

RESUMO

OBJECTIVE: Patients with non-ST elevation acute coronary syndrome (NSTE-ACS) benefit from coronary intervention, but the optimal timing for an invasive strategy is not well defined. This study aimed to determine whether an early invasive strategy (<12 hours) is superior to a delayed invasive strategy. METHODS: Twelve studies of nine randomized, controlled trials of 8586 patients were included. RESULTS: There were no significant differences in all-cause death (risk ratio [95% confidence interval]) (0.90, [0.77-1.06), re-myocardial infarction (re-MI) (0.95 [0.70-1.29]), major bleeding (0.97 [0.77-1.23]), and refractory ischemia (0.74 [0.53-1.05]) when we compared use of early and delayed invasive strategies. Furthermore, analysis of the effect of the chosen strategy on high-risk patients showed that the rate of composite death or re-MI was significantly decreased in patients with either a Global Registry of Acute Coronary Events (GRACE) risk score >140 or with elevated troponin levels (risk ratio 0.82 [0.72-0.92]; risk ratio 0.84 [0.76-0.93], respectively). CONCLUSIONS: This meta-analysis shows that an early angiographic strategy does not improve clinical outcome in patients with NSTE-ACS. An early invasive strategy might reduce the rate of composite death or re-MI in high-risk patients with GRACE risk scores >140 or elevated cardiac markers.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Angiografia Coronária , Humanos , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento
5.
Mol Med Rep ; 22(4): 2617-2626, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32945433

RESUMO

Moderate hypothermia plays a major role in myocardial cell death as a result of hypoxia/reoxygenation (H/R) injury. However, few studies have investigated the molecular mechanisms of hypothermic cardioprotection. Several responses to stress and other cell functions are regulated by post­translational protein modifications controlled by small ubiquitin­like modifier (SUMO). Previous studies have established that high SUMOylation of proteins potentiates the ability of cells to withstand hypoxic­ischemic stress. The level to which moderate hypothermia affects SUMOylation is not fully understood, as the functions of SUMOylation in the heart have not been studied in depth. The aim of the present study was to investigate the effect of moderate hypothermia (33˚C) on the protective functions of SUMOylation on myocardial cells. HL­1 and H9c2 cells were treated with the hypoxia­mimetic chemical CoCl2 and complete medium to simulate H/R injury. Hypothermia intervention was then administered. A Cell Counting kit­8 assay was used to analyze cell viability. Mitochondrial membrane potential and the generation of reactive oxygen species (ROS) were used as functional indexes of mitochondria dysfunction. Bcl­2 and caspase­3 expression levels were analyzed by western blotting. The present results suggested that moderate hypothermia significantly increased SUMO1 and Bcl­2 expression levels, as well as the mitochondrial membrane potential, but significantly decreased the expression levels of caspase­3 and mitochondrial ROS. Thus, moderate hypothermia may enhance SUMOylation and attenuate myocardial H/R injury. Moreover, a combination of SUMOylation and moderate hypothermia may be a potential cardiovascular intervention.


Assuntos
Caspase 3/metabolismo , Cobalto/efeitos adversos , Hipotermia Induzida/métodos , Miócitos Cardíacos/citologia , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína SUMO-1/metabolismo , Animais , Técnicas de Cultura de Células , Hipóxia Celular , Linhagem Celular , Sobrevivência Celular , Regulação da Expressão Gênica , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Modelos Biológicos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sumoilação
6.
Coron Artery Dis ; 27(6): 467-77, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27100660

RESUMO

AIM: The aim of this meta-analysis was to evaluate the efficacy of drug-eluting balloons (DEBs) plus bare-metal stents (BMS) for the treatment of de-novo coronary lesions. METHODS AND RESULTS: Eleven trials involving 1279 patients were included in this study. The main endpoints were as follows: late lumen loss (LLL), binary restenosis, stent thrombosis (ST), and major adverse cardiovascular events (MACEs). The definition of MACEs was a composite of death, myocardial infarction (MI), and target lesion revascularization (TLR). Compared with BMS alone, DEB plus BMS showed a lower risk for LLL (P=0.007) and MACEs (P=0.010). There were no significant differences in binary restenosis (P=0.212), ST (P=0.199), death (P=0.141), MI (P=0.439), and TLR (P=0.340). Compared with drug-eluting stents (DES), DEB plus BMS could increase the risk of LLL (P=0.002) and MACEs (P=0.026). The risks of binary restenosis (P=0.113), ST (P=0.832), death (P=0.115), MI (P=0.831), and TLR (P=0.111) were similar between DEB plus BMS and DES. CONCLUSION: DEB plus BMS was better than BMS alone in reducing LLL and MACEs, especially when dilatation was performed after stenting for de-novo coronary lesions, but it was inferior to DES. Therefore, the treatment strategy with DEB plus BMS should not be recommended for de-novo coronary lesions, except for patients who have contraindications for DES.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Cateteres Cardíacos , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana/terapia , Paclitaxel/administração & dosagem , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/mortalidade , Fármacos Cardiovasculares/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Reestenose Coronária/etiologia , Trombose Coronária/etiologia , Humanos , Metais , Infarto do Miocárdio/etiologia , Razão de Chances , Paclitaxel/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento
7.
Int J Clin Exp Med ; 8(4): 5553-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26131137

RESUMO

OBJECTIVE: This study aims to explore the role of leptin in the ventricular remodeling process and its mechanism in the diabetic rats' model. METHODS: The diabetic SD rats model induced by streptozotocin was established. The SD rats were randomly divided into 4 groups: control group (20 rats treated with citric acid/sodium citrate buffer); M0 group (10 rats treated with physiological saline); M1 group (10 rats treated with 50 µg/kg LP); M2 group (10 rats treated with 100 µg/kg LP). Ang-II was detected by ELISA. The expression levels of LP and Ob-Rb were detected by RT-PCR. MAPK phosphorylation changes were detected by western blotting. Myocardial morphology was observed. RESULTS: Compared with control group, the blood glucose concentration and Ang-II significantly increased in diabetic model groups (P < 0.01) and body weight decreased (P < 0.05). The expression levels of LP and Ob-Rb increased and heart function decreased in diabetic model groups. CONCLUSIONS: LP may be involved in the myocardial cell hypertrophy through the neuroendocrine system and associated with the JAK-STAT, Ras-Raf-MEK-MAPK and PI-3K signaling pathway, which provides a new concept for the pathogenesis of cardiac hypertrophy.

8.
Cell Biochem Biophys ; 70(2): 1205-11, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24906234

RESUMO

Coronary angiography is the gold standard for the diagnosis of coronary artery disease. Coronary artery Gensini scoring systems measure both the extent and the degree of stenosis of coronary artery and therefore, give clinicians a more accurate, objective, and comprehensive assessment of the severity of coronary artery disease. Using Gensini scoring systems in combination with statistical analysis, we found that five variables, namely, Brachial-ankle pulse wave velocity (PWV), ankle-brachial index (ABI), carotid artery intima-media thickness (IMT), blood sugar, and high density lipoprotein cholesterol (HDL-C), were all significantly different among groups of patients with different Gensini scores. All five variables can be used for early screening and assessment of coronary artery disease as independent prognostic factors for the morbidity and mortality from cardiovascular conditions. With the progression of coronary artery disease, the levels of PWV, IMT, and blood glucose are gradually increasing whereas the levels of ABI and HDL-C are gradually decreasing. These changes can be treated as warning signs and can also be helpful in evaluating the severity of coronary artery diseases. It is highly recommended to perform these five non-invasive tests as early as possible in order to identify high-risk patients at their subclinical stages. This would allow timely intervention and thereby lead to reduced morbidity and mortality from cardiovascular diseases.


Assuntos
Índice Tornozelo-Braço , Artéria Braquial/fisiopatologia , Espessura Intima-Media Carotídea , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Análise de Onda de Pulso , Idoso , Glicemia/metabolismo , Artéria Braquial/diagnóstico por imagem , HDL-Colesterol/sangue , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade
9.
Zhonghua Yi Xue Za Zhi ; 91(4): 272-6, 2011 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-21418875

RESUMO

OBJECTIVE: To explore the role of homocysteine in the pathogenesis of alcoholic cardiomyopathy. METHODS: A total of 69 male Wistar rats were randomly assigned into two groups: alcohol-fed group and the control. Cardiac function was assessed by pulse Doppler. Plasma Hcy levels were examined using automatic biochemical instrument (chemiluminescence). The protein expression of MMP-9 was evaluated using immunohistochemical method, and collagen fiber of myocardium was quantitative analyzed by Masson stain. RESULTS: After heavy drinking, the LVEDd of alcohol-fed group were larger than the control group [(7.0±0.6) mm vs (5.0±0.4) mm, P<0.05], the LVEF and FS were lower in the 4th month (52%±8% vs 78%±4%, 31%±3% vs 47%±2%, P<0.05), the data changed more significantly (P<0.01) in the 6th month. The level of plasma Hcy from alcohol-fed group was significantly higher from the 2nd month than that before the experiment [(18.1±3.1) µmol/L vs (9.8±2.1) µmol/L, P<0.01], and it was higher in 4th month than that in 2nd month [(26.3±4.0) µmol/L vs (18.1±3.1) µmol/L, P<0.05], it was highest in 6 months. After 4-month and 6-month drinking, the expression of MMP-9 protein from alcohol group was higher than before the experiment (0.161%±0.019%, 0.263%±0.014% vs 0.050%±0.008%, P<0.01). Masson staining showed myocardial collagen of alcohol group was more after 4-month and 6-month drinking than those before the experiment (10.23%±1.20% vs 0.50%±0.09%; 22.41%±2.57% vs 0.50%±0.09%, P<0.01). Plasma Hcy and cardiac tissue MMP-9 is a significant positive correlation (r=0.848, P<0.01). CONCLUSION: Long-term and large drink liquor can lead to plasma Hcy levels significantly increased, and participate cardiac remodeling and the pathogenesis of ACM through increasing the expression of myocardial tissue MMP-9 protein.


Assuntos
Cardiomiopatia Alcoólica/metabolismo , Homocisteína/sangue , Miocárdio/metabolismo , Animais , Cardiomiopatia Alcoólica/patologia , Cardiomiopatia Alcoólica/fisiopatologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Ratos , Ratos Wistar
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