RESUMO
Hyperglycemia-induced cardiac fibrosis is a prominent characteristic of diabetic cardiomyopathy. Changes in proinflammatory cytokines have been shown to lead to cardiac fibrosis in patients with diabetes mellitus. This study aimed to investigate the role of miR-150-5p in mediating cardiac inflammation and fibrosis in cardiac fibroblasts (CFs). Herein, we found that high-glucose (HG) treatment significantly induced cardiac inflammation, as manifested by increased proinflammatory cytokine production (IL-1ß) and NF-κB activity in CFs. Moreover, HG markedly aggravated cardiac fibrosis and increased levels of fibrotic markers (CTGF, FN, α-SMA) and extracellular matrix proteins (Col-I, Col-III) in CFs. At the same time, HG disturbed the TGF-ß1/Smad signaling pathway, as evidenced by increases in TGF-ß1 and p-Smad2/3 levels and decreases in Smad7 levels in CFs. Furthermore, we found that miR-150-5p was upregulated by HG, which negatively regulated Smad7 expression at the posttranscription level. Further study demonstrated that cardiac inflammation and fibrosis in CFs were corrected following miR-150-5p knockdown, but exacerbated by miR-150-5p overexpression. These data indicated that miR-150-5p inhibition could ameliorate NF-κB-related inflammation and TGF-ß1/Smad-induced cardiac fibrosis through targeting Smad7. Thus, miR-150-5p may be a novel promising target for treating diabetic cardiomyopathy.
Assuntos
Cardiomiopatias Diabéticas/metabolismo , Fibroblastos/patologia , Glucose/toxicidade , MicroRNAs/metabolismo , Proteína Smad7/metabolismo , Animais , Células Cultivadas , Cardiomiopatias Diabéticas/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose , Regulação da Expressão Gênica , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
Background: Myocardial microcirculation dysfunction is the most potent predictor of adverse cardiovascular events in hypertension. The current study aimed to apply intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) to assess hypertension-related microcirculation dysfunction. Methods: In this prospective study, 102 participants were recruited from our hospital and underwent cardiac magnetic resonance (CMR) examination on a 3T scanning system. Hypertensive patients were divided into 3 subgroups based on blood pressure (BP) types. Two experienced CMR radiologists independently analyzed all images, and Bland-Altman analysis was applied to assess intra- and inter-observer reproducibility. Cardiac function indexes and IVIM-DWI parameters were compared between the hypertension and healthy control groups, as well as among the three hypertension subgroups. Results: Totally 62 participants with hypertension and 27 healthy controls were included. 13 participants were excluded for poor quality of IVIM-DWI images. Significantly higher maximal left ventricular wall thickness (10.3±2.0 vs. 8.6±1.4 mm, P<0.001) and left ventricular mass index (49.0±9.1 vs. 42.1±7.5 g/m2, P<0.05) were observed inhypertension group compared with healthy control group. There were significant statistical differences in pseudo diffusion (D*) between them (81.3±16.3 vs. 111.8±18.9 mm2/s, P<0.001), as well as among the three hypertension subgroups (99.4±13.9 vs. 79.7±10.6 vs. 67.1±6.6 mm2/s, P<0.001). Participants with poor quality of IVIM-DWI images had higher heart rates (72.2±10.0 vs. 62.0±8.1 bpm, P<0.001). Conclusions: IVIM-DWI is feasible for quantitatively evaluating myocardial microcirculation dysfunction in hypertension. The D* parameter has a potential value for assessing the severity of microcirculation dysfunction in different BP categories.
RESUMO
The genome of unicellular green alga Chlamydomonas reinhardtii contains four genes encoding B-type methionine sulfoxide reductases, MSRB1.1, MSRB1.2, MSRB2.1, and MSRB2.2, with functions largely unknown. To understand the cell defense system mediated by the methionine sulfoxide reductases in Chlamydomonas, we analyzed expression and physiological roles of the MSRBs under different abiotic stress conditions using immunoblotting and quantitative polymerase chain reaction (PCR) analyses. We showed that the MSRB2.2 protein was accumulated in cells treated with high light (1,300 µE/m² per s), whereas MSRB1.1 was accumulated in the cells under 1 mmol/L H2O2 treatment or sulfur depletion. We observed that the cells with the MSRB2.2 knockdown and overexpression displayed increased and decreased sensitivity to high light, respectively, based on in situ chlorophyll a fluorescence measures. We also observed that the cells with the MSRB1.1 knockdown and overexpression displayed decreased and increased tolerance to sulfur-depletion and oxidative stresses, respectively, based on growth and H2-producing performance. The physiological implications revealed from the experimental data highlight the importance of MSRB2.2 and MSRB1.1 in protecting Chlamydomonas cells against adverse conditions such as high-light, sulfur-depletion, and oxidative stresses.
Assuntos
Chlamydomonas/enzimologia , Chlamydomonas/efeitos da radiação , Luz , Metionina Sulfóxido Redutases/metabolismo , Estresse Oxidativo/efeitos da radiação , Enxofre/deficiência , Formação de Anticorpos , Chlamydomonas/efeitos dos fármacos , Chlamydomonas/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Peróxido de Hidrogênio/farmacologia , Metionina Sulfóxido Redutases/química , Metionina Sulfóxido Redutases/genética , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Plantas Geneticamente Modificadas , Análise de Sequência de Proteína , Estresse Fisiológico/efeitos da radiaçãoRESUMO
The aim of the study was to determine the effect of tetramethylpyrazine phosphate tablets (TPT), a Chinese medicine used for cardiovascular disease, on immunity activity and oxidative injury in rats. Heart failure (HF) was induced by isoproterenol (ISO). After the animal model was established, the rats were administered the TPT by gavage (once a day). The results indicated that TPT improved left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dP/dt, heart weight/body weight. TPT could decrease the levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). Furthermore, it also could raise the activities of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but reduce malonyldialdehyde (MDA) level. The results indicated that TPT improved cardiac function and myocardial fibrosis from myocardial injury, and this cardioprotection might be attributed to a reduction of oxidative stress and regulation of inflammation mediators.
Assuntos
Antioxidantes/uso terapêutico , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Organofosfatos/uso terapêutico , Pirazinas/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Coração/efeitos dos fármacos , Coração/fisiopatologia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/metabolismo , Interleucina-6/biossíntese , Interleucina-6/imunologia , Isoproterenol , Malondialdeído/análise , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Comprimidos , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologia , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
The green alga Chlamydomonas reinhardtii is a model organism to study H(2) metabolism in photosynthetic eukaryotes. To understand the molecular mechanism of H(2) metabolism, we used 2-DE coupled with MALDI-TOF and MALDI-TOF/TOF-MS to investigate proteomic changes of Chlamydomonas cells that undergo sulfur-depleted H(2) photoproduction process. In this report, we obtained 2-D PAGE soluble protein profiles of Chlamydomonas at three time points representing different phases leading to H(2) production. We found over 105 Coomassie-stained protein spots, corresponding to 82 unique gene products, changed in abundance throughout the process. Major changes included photosynthetic machinery, protein biosynthetic apparatus, molecular chaperones, and 20S proteasomal components. A number of proteins related to sulfate, nitrogen and acetate assimilation, and antioxidative reactions were also changed significantly. Other proteins showing alteration during the sulfur-depleted H(2) photoproduction process were proteins involved in cell wall and flagella metabolisms. In addition, among these differentially expressed proteins, 11 were found to be predicted proteins without functional annotation in the Chlamydomonas genome database. The results of this proteomic analysis provide new insight into molecular basis of H(2) photoproduction in Chlamydomonas under sulfur depletion.
Assuntos
Chlamydomonas reinhardtii/fisiologia , Hidrogênio/metabolismo , Fotossíntese/fisiologia , Proteínas de Plantas/isolamento & purificação , Proteômica/métodos , Enxofre/deficiência , Chlamydomonas reinhardtii/metabolismo , Eletroforese em Gel Bidimensional , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Corantes de Rosanilina , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
The cardioprotective effects of moderate alcohol consumption and statins have been known for years. However, heavy or binge drinking confers a high risk of cardiovascular disease. This study aimed to investigate the effects of different levels of alcohol consumption on acute myocardial infarction that was induced experimentally in rats, with a focus on the potential mechanism of angiogenesis and the effects of statins on heavy drinking. The experimental rats were fed low-dose ethanol (0.5 g/kg/day), high-dose ethanol (5 g/kg/day), and high-dose ethanol with rosuvastatin (10 mg/kg/day) during the entire experiment. Acute myocardial infarctions were induced 4 weeks after the beginning of the experiment. We assessed the capillary density in the myocardium via immunohistochemistry and quantified the expression of vascular endothelial growth factor (VEGF) and endostatin via enzyme-linked immunosorbent assay kits on the 4th day after myocardial infarction. The results revealed that low ethanol consumption promoted angiogenesis in association with higher VEGF and lower endostatin. High ethanol intake suppressed angiogenesis with unchanged VEGF and elevated endostatin. Treatment with rosuvastatin preserved angiogenesis following high ethanol intake, with an upregulation of VEGF. This study highlights that low ethanol consumption obviously promotes angiogenesis in myocardial-infarction rats while increasing the expression of VEGF, whereas high ethanol consumption inhibits ischemia-induced angiogenesis. This study also provides evidence that rosuvastatin alleviates the inhibitory effects of heavy drinking on angiogenesis.
Assuntos
Cardiotônicos/farmacologia , Etanol/administração & dosagem , Etanol/farmacologia , Infarto do Miocárdio/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , Rosuvastatina Cálcica/farmacologia , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Endostatinas/metabolismo , Etanol/antagonistas & inibidores , Coração/fisiologia , Masculino , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The aim of this study was to explore the correlation of erythropoietin (EPO) with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hs-CRP) in patients with chronic heart failure (CHF) or CHF complicated with anemia, in addition to its correlation with the prognosis of the patient. A total of 217 CHF patients were enrolled in this study. The patients were graded according to the cardiac function criteria of the New York Heart Association (NYHA). The serum EPO, NT-proBNP and hs-CRP levels of the patients were determined. The patients were followed up for ≥24 months. The EPO expression level in patients with NYHA II-IV CHF was significantly higher compared with that in the control group (P<0.05). EPO expression increased with the aggravation of CHF, exhibiting significant differences amongst the various NYHA graded groups (P<0.05). The EPO expression level increased significantly with an increase in NHA grade in addition to the severity of the anemia in the patients with CHF complicated by anemia (P<0.05). In the patients who succumbed (mortality group), the expression level of EPO was significantly higher and the hemoglobin level was significantly lower compared with those of the survival group (P<0.05). The EPO expression levels were elevated in CHF patients and patients with CHF and anemia. The level of expression correlated positively with the severity of CHF as well as that of anemia. Serum EPO measurements were successful in predicting the mortality and re-hospitalization rates of CHF patients at the end point, within two years of follow-up.
RESUMO
Cadmium (Cd) is highly toxic to all organisms. Soil contamination by Cd has become an increasing problem worldwide due to the intensive use of Cd-containing phosphate fertilizers and industrial zinc mining. Phytolacca americana L. is a Cd hyperaccumulator plant that can grow in Cd-polluted areas. However, the molecular basis for its remarkable Cd resistance is not known. In this study, the effects of Cd exposure on protein expression patterns in P.americana was investigated by 2-dimensional gel electrophoresis (2-DE). 2-DE profiles of leaf proteins from both control and Cd-treated (400µM, 48h) seedlings were compared quantitatively using ImageMaster software. In total, 32 differentially expressed protein spots were identified using MALDI-TOF/TOF mass spectrometry coupled to protein database search, corresponding to 25 unique gene products. Of those 14 were enhanced/induced while 11 reduced under Cd treatment. The alteration pattern of protein expression was verified for several key proteins involved in distinct metabolic pathways by immuno-blot analysis. Major changes were found for the proteins involved in photosynthetic pathways as well as in the sulfur- and GSH-related metabolisms. One-third of the up-regulated proteins were attributed to transcription, translation and molecular chaperones including a protein belonging to the calreticulin family. Other proteins include antioxidative enzymes such as 2-cys-peroxidase and oxidoreductases. The results of this proteomic analysis provide the first and primary information regarding the molecular basis of Cd hypertolerance in P. americana.