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1.
J Clin Hypertens (Greenwich) ; 21(12): 1813-1820, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31670874

RESUMO

This was a post hoc analysis of Systolic Blood Pressure Intervention Trial (SPRINT), aimed to investigate whether intensive blood pressure treatment has differential therapeutic outcomes on patients with different baseline Framingham risk score (FRS). The 9298 SPRINT participants were categorized into low-risk (baseline FRS < 10%), intermediate-risk (FRS = 10%-20%), or high-risk (FRS > 20%) arms. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Serious adverse events were defined as hypotension, syncope, and bradycardia. Multiple Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these three groups. After a median follow-up time of 3.26 years, the primary outcome hazard ratio (HR) for intensive versus standard treatment was 0.73 (95% CI: 0.61-0.88, P = .0044) in the high-risk arm. And, for all-cause mortality, the hazard ratio with intensive SBP treatment was 1.58 (95% CI: 0.55-1.06), 0.9 (95% CI: 0.26-9.50), and 0.53 (95% CI: 0.34-0.82) in three arms (all P values for interaction > 0.05). Effects of intensive versus standard SBP control on serious adverse events were similar among patients with different FRS. Our results suggested that regardless of the FRS level, the intensive blood pressure control was beneficial.

2.
Clin Cardiol ; 42(12): 1170-1180, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31609463

RESUMO

BACKGROUND: Dual antiplatelet therapy (DAPT) in the form of aspirin plus a P2 Y12 inhibitor, when indicated, is one of the key treatments in coronary artery disease (CAD). Many recommendations on DAPT in patients with CAD based on current guidelines are largely inconsistent. In our current study, we aimed at systematically reviewing DAPT-relevant clinical practice guidelines, and highlighting their commonalities and differences for better informed decision-making. METHODS: Contemporary guidelines in English were searched in MEDLINE, Embase and websites of guideline organizations and professional societies. Guidelines with recommendations on DAPT for CAD patients were included. Guideline quality was appraised with the 6-domain Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. The reporting of conflicts of interest (COI) was assessed individually with supplementary items from the RIGHT (Reporting Item for Practice Guidelines in Healthcare) checklist. Meanwhile, extraction of recommendations was performed. RESULTS: A total of 18 guidelines fulfilled our inclusion criteria. Most of them were graded with relatively good scores averaging from 42% to 74%. Domains for lower scores were in "stakeholder involvement" and "application." The reporting of COI was satisfactory. For the recommendations on DAPT, most guidelines with high AGREE II scores included consistent recommendations on the timing and P2 Y12 inhibitor selection. Nonetheless, conflicts still exist on the duration of DAPT. CONCLUSIONS: Quality of guidelines for DAPT in CAD was relatively high, though defects existed in "Applicability" and "Stakeholder Involvement." As these guidelines developed, DAPT recommendations gradually converged on a consensus. Clinical decision should be made on an individual basis.

3.
Diabetes Care ; 42(12): 2334-2337, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31548243

RESUMO

OBJECTIVE: To determine whether visit-to-visit fasting glucose (VVFG) variability in young adulthood is associated with midlife hippocampal integrity and volume. RESEARCH DESIGN AND METHODS: Multivariable-adjusted linear regression models were used to estimate the association between VVFG variability and brain MRI variables in 543 CARDIA study participants. VVFG variability was defined by the SD of FG (SDFG), the coefficient of variation of the mean FG (CVFG), and the average real variability (ARVFG) over 25 years of follow-up. Hippocampal integrity fractional anisotropy (FA) and tissue volume standardized to intracranial volume were measured by 3T MRI at year 25. RESULTS: After multivariable adjustment, higher FG variability (1-SD increase) was associated with lower hippocampal FA (SDFG -0.015 [95% CI -0.026, -0.004]; CVFG -0.009 [95% CI -0.018, -0.001]; ARVFG -0.011 [95% CI -0.019, -0.002]) and lower hippocampal volume (SDFG -0.012 [95% CI -0.023, -0.001]). CONCLUSIONS: Higher VVFG variability in young adulthood is associated with lower midlife hippocampal integrity and volume, suggesting its value in predicting risk for hippocampal structural damage.

4.
J Thorac Dis ; 11(8): 3534-3546, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31559060

RESUMO

Background: Clinical practice guidelines (CPGs) provide many recommendations for hyperlipidemia management, but some of them are still debatable. Methods: We applied the six-domain Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument to evaluate the quality of guidelines with lipid management recommendations for coronary heart disease (CHD), including dyslipidemia and CHD guidelines published from 2009 to 2019. Meanwhile, we synthesized and compared major recommendations and present the consistency and controversy in current dyslipidemia management. Results: Among 19 guidelines included, ten guidelines ("strongly recommended" with AGREE scores 61-94%) performed better than the other nine (38-65% as "recommended with some modification") For blood lipid tests, most CHD guidelines simply required fasting sample while dyslipidemia guidelines preferred non-fasting sample except in high triglycerides state. Most guidelines consistently chose low-density lipoprotein cholesterol (LDL-C) as the primary lipid-lowering target (LLT), while non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B were mainly selected as secondary LLTs. The specific goals of LDL-C lowering were either to lower than 70 mg/dL or with at least 50% reduction. All guidelines recommended high intensity or maximally tolerable doses of statins, while ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were recommended as second-line therapy. Conclusions: The general quality of guidelines for lipid management is satisfactory. Consensus has been reached on the specific goal of lipid reduction and the intensity of statins therapy. Further research is needed to validate the application of non-fasting sample and non-HDL-C target, as well as the efficacy and safety of ezetimibe and PCSK9 inhibitors.

5.
Eur J Prev Cardiol ; 26(16): 1693-1706, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31213079

RESUMO

BACKGROUND: Hypertensive patients are highly heterogeneous in cardiovascular prognosis and treatment responses. A better classification system with phenomapping of clinical features would be of greater value to identify patients at higher risk of developing cardiovascular outcomes and direct individual decision-making for antihypertensive treatment. METHODS: An unsupervised, data-driven cluster analysis was performed for all baseline variables related to cardiovascular outcomes and treatment responses in subjects from the Systolic Blood Pressure Intervention Trial (SPRINT), in order to identify distinct subgroups with maximal within-group similarities and between-group differences. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular outcomes and compare the effect of intensive antihypertensive treatment in different clusters. RESULTS: Four replicable clusters of patients were identified: cluster 1 (index hypertensives); cluster 2 (chronic kidney disease hypertensives); cluster 3 (obese hypertensives) and cluster 4 (extra risky hypertensives). In terms of prognosis, individuals in cluster 4 had the highest risk of developing primary outcomes. In terms of treatment responses, intensive antihypertensive treatment was shown to be beneficial only in cluster 4 (HR 0.73, 95% CI 0.55-0.98) and cluster 1 (HR 0.54, 95% CI 0.37-0.79) and was associated with an increased risk of severe adverse effects in cluster 2 (HR 1.18, 95% CI 1.05-1.32). CONCLUSION: Using a data-driven approach, SPRINT subjects can be stratified into four phenotypically distinct subgroups with different profiles on cardiovascular prognoses and responses to intensive antihypertensive treatment. Of note, these results should be taken as hypothesis generating that warrant further validation in future prospective studies.

6.
J Am Heart Assoc ; 8(9): e011955, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31020911

RESUMO

Background The influences of low-carbohydrate diets in cardiovascular disease are controversial. Few studies have examined the relationship of carbohydrate intake and risk of incident atrial fibrillation ( AF ). We aimed to evaluate the association between carbohydrate intake and the risk of incident AF in the ARIC (Atherosclerosis Risk in Communities) Study. Methods and Results We included 13 385 participants (age, 54.2±5.8 years; 45.1% men and 74.7% white) who completed a dietary questionnaire at baseline (1987-1989) in the ARIC Study. The primary outcome was incident AF , which was identified by ECG performed during study examinations, hospital discharge codes, and death certificates. We used multivariable Cox hazard regression models to assess the association between carbohydrate intake and incident AF . We further explored the effects of specific food source (animal versus plant based) used to replace carbohydrate intake in the low-carbohydrate intake setting. During a median follow-up of 22.4 years, 1808 cases (13.5%) of AF occurred. The hazard ratio for incident AF associated with a 1- SD (9.4%) increase in carbohydrate intake as a percentage of energy intake was 0.82 (95% CI , 0.72-0.94), after adjustment for traditional AF risk factors and other diets factors. Results were similar when individuals were categorized by carbohydrate intake quartiles (hazard ratio, 0.64; 95% CI , 0.49-0.84; comparing extreme quartiles). No association was found between the type of protein or fat used to replace the carbohydrate and risk of incident AF . Conclusions Low-carbohydrate diets were associated with increased risk of incident AF , regardless of the type of protein or fat used to replace the carbohydrate.

7.
Atherosclerosis ; 282: 196-201, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30658844

RESUMO

BACKGROUND AND AIMS: Peripheral arterial disease (PAD) is a clinical manifestation of extracoronary atherosclerosis. Many risk factors are involved in the process of PAD, but the association between serum magnesium (Mg) and PAD is not clear. Our study aimed to investigate whether serum Mg is associated with PAD incidence. METHODS: A total of 13,826 participants (aged 40-64 years) in the Atherosclerosis Risk in Communities (ARIC) study (1987-1989) without prior PAD were included in the final analysis. Serum Mg levels were measured at visits 1 and 2. PAD was defined as an ankle brachial index less than 0.9, or hospitalization with a PAD diagnosis. Cox regression was used to calculate hazard ratios (HRs) for incidence of PAD and serum Mg. RESULTS: During a median follow-up of 24.4 years, 1364 (48.4% female) PAD events were observed. After multiple adjustment, participants in the lowest (≤1.4 mEq/L) category of serum Mg compared with the highest (≥1.8 mEq/L) ones were at higher PAD risk (HR: 1.3; 95% confidence interval (CI): 1.06-1.58) (p value = 0.004). The HRs for PAD in 1.5, 1.6 and 1.7 mEq/L of serum Mg were 1.29 (95% CI: 1.08-1.54), 1.05 (95% CI: 0.89-1.24), and 1.0 (95% CI: 0.85-1.18), respectively. CONCLUSIONS: Low serum Mg was independently associated with an increased prevalence of PAD in the large population-based study; further studies are needed to confirm our findings.

8.
Clin Res Cardiol ; 108(3): 273-281, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30167807

RESUMO

OBJECTIVE: To determine whether the effects of intensive (< 120 mmHg) compared with standard (< 140 mmHg) systolic blood pressure (SBP) treatments are different among those with different baseline SBP. METHODS: De-identified SPRINT database was used for this post hoc analysis. SPRINT participants were categorized by baseline SBP status, defined as high-SBP (≥ 140 mmHg) group versus the low-SBP (< 140 mmHg) group. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Treatment-related adverse events including hypotension, syncope, and bradycardia were also evaluated. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these two groups. RESULTS: Among 9361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 4964 and 4397 had baseline low SBP (< 140 mmHg) and high SBP (≥ 140 mmHg), respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.65 (95% CI 0.50, 0.83) and 0.84 (95% CI 0.66, 1.06) among those in the low-SBP group and high-SBP group, respectively (P value for interaction 0.15). For treatment-related adverse events, the hazard ratio with intensive SBP treatment was 2.03 (95% CI 1.44, 2.85) for the low-SBP group and 1.80 (95% CI 1.32, 2.47) for the high-SBP group (P value for interaction 0.28). CONCLUSIONS: Hypertensive patients with low baseline SBP may benefit from intensive SBP lowering, whereas benefits were inconclusive among those with high baseline SBP.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Hipertensão/tratamento farmacológico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Determinação da Pressão Arterial , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Incidência , Masculino , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Porto Rico/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Taxa de Sobrevida/tendências , Sístole , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
9.
Environ Int ; 118: 146-153, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29879615

RESUMO

OBJECTIVES: An environment-wide association study (EWAS) may be useful to comprehensively test and validate associations between environmental factors and cardiovascular disease (CVD) in an unbiased manner. APPROACH AND RESULTS: Data from National Health and Nutrition Examination Survey (1999-2014) were randomly 50:50 spilt into training set and testing set. CVD was ascertained by a self-reported diagnosis of myocardial infarction, coronary heart disease or stroke. We performed multiple linear regression analyses associating 203 environmental factors and 132 clinical phenotypes with CVD in training set (false discovery rate < 5%) and significant factors were validated in the testing set (P < 0.05). Random forest (RF) model was used for multicollinearity elimination and variable importance ranking. Discriminative power of factors for CVD was calculated by area under the receiver operating characteristic (AUROC). Overall, 43,568 participants with 4084 (9.4%) CVD were included. After adjusting for age, sex, race, body mass index, blood pressure and socio-economic level, we identified 5 environmental variables and 19 clinical phenotypes associated with CVD in training and testing dataset. Top five factors in RF importance ranking were: waist, glucose, uric acid, and red cell distribution width and glycated hemoglobin. AUROC of the RF model was 0.816 (top 5 factors) and 0.819 (full model). Sensitivity analyses reveal no specific moderators of the associations. CONCLUSION: Our systematic evaluation provides new knowledge on the complex array of environmental correlates of CVD. These identified correlates may serve as a complementary approach to CVD risk assessment. Our findings need to be probed in further observational and interventional studies.


Assuntos
Doenças Cardiovasculares/epidemiologia , Exposição Ambiental , Área Sob a Curva , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Exposição Ambiental/análise , Exposição Ambiental/estatística & dados numéricos , Humanos , Inquéritos Nutricionais , Estados Unidos/epidemiologia , Ácido Úrico/análise
10.
Int J Mol Med ; 42(2): 1199, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29749426

RESUMO

Subsequently to the publication of this article, the authors have realized that an address affiliation associated with certain of the authors had been omitted. The authors' affiliation information should have appeared as follows (the omitted address affiliation is featured in bold): Yi­Ying Yang1,2*, Xiu­Ting Sun1,2*, Zheng­Xun Li1,2, Wei­Yan Chen3, Xiang Wang4, Mei­Ling Liang5, Hui Shi1,2, Zhi­Sheng Yang1,2 and Wu­Tao Zeng1,2 1Department of Cardiology, The First Affiliated Hospital, Sun Yat­Sen University; 2Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou, Guangdong 510080; 3Intensive Care Unit, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260; 4Department of Cardiology, Laiwu City People's Hospital, Laiwu, Shandong 27110; 5Department of Cardiology, Sun Yat­Sen Cardiovascular Hospital, Shenzhen, Guangdong 518020, P.R. China *Contributed equally. The authors regret this error in the affiliations, and apologize for any inconvenience caused. [the original article was published in the International Journal of Molecular Medicine 41: 1283­1292, 2018; DOI: 10.3892/ijmm.2017.3322].

11.
Int J Mol Med ; 41(3): 1283-1292, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29286068

RESUMO

Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide mainly generated from cleavage of AngⅠ and AngⅡ, possesses physiological and pharmacological properties, including anti­inflammatory and antidiabetic properties. Activation of the phosphoinositide 3-kinase and protein kinase B (PI3K̸Akt) signaling pathway has been confirmed to participate in cardioprotection against hyperglycaemia-induced injury. The aim of the present study was to test the hypothesis that Ang-(1-7) protects H9c2 cardiomyoblast cells against high glucose (HG)-induced injury by activating the PI3K̸Akt pathway. To examine this hypothesis, H9c2 cells were treated with 35 mmol/l (mM) glucose (HG) for 24 h to establish a HG-induced cardiomyocyte injury model. The cells were co-treated with 1 µmol/l (µM) Ang-(1-7) and 35 mM glucose. The findings of the present study demonstrated that exposure of H9c2 cells to HG for 24 h markedly induced injury, as evidenced by an increase in the percentage of apoptotic cells, generation of reactive oxygen species and level of inflammatory cytokines, as well as a decline in cell viability and mitochondrial luminosity. These injuries were significantly attenuated by co-treatment of the cells with Ang-(1-7) and HG. In addition, PI3K̸Akt phosphorylation was suppressed by HG treatment, but this effect was abolished when the H9c2 cells were co-treated with Ang-(1-7) and HG. Furthermore, the cardioprotection of Ang-(1-7) against HG-induced injury in H9c2 cardiomyoblasts was highly attenuated in the presence of either D-Ala7-Ang-(1-7) (A-779, an antagonist of the Mas receptor) or LY294002 (an inhibitor of PI3K̸Akt). In conclusion, the present study provided new evidence that Ang-(1-7) protects H9c2 cardiomyoblasts against HG-induced injury by activating the PI3K̸Akt signaling pathway.


Assuntos
Angiotensina I/farmacologia , Cardiotônicos/farmacologia , Hiperglicemia/patologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Fragmentos de Peptídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Glucose/toxicidade , Inflamação/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo
12.
Mol Med Rep ; 17(1): 1461-1468, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29257199

RESUMO

The transplantation of mesenchymal stem cells (MSCs) has been a reported method for alleviating atherosclerosis (AS). Because the availability of bone marrow­derived MSCs (BM­MSCs) is limited, the authors used this study to explore the use of a new type of MSC, human induced pluripotent stem cell­derived MSCs (iPSC­MSCs), to evaluate whether these cells could alleviate AS. iPSC­MSCs were intravenously administered to ApoE knock out mice fed on a high­fat diet (HFD) for 12 weeks. It was reported that systematically administering iPSC­MSCs clearly reduced the size of plaques. In addition, the numbers of macrophages and lipids in plaques were lower in the HFD + iPSC­MSCs group than in the HFD group. Furthermore, iPSC­MSCs attenuated AS­associated inflammation by decreasing the levels of inflammatory cytokines, such as tumor necrosis factor­α and interleukin­6, in serum. In addition, the expression of Notch1 was higher in the HFD group, and injecting iPSC­MSCs reversed this effect. In conclusion, the current study provides the first evidence indicating that iPSC­MSCs may be a new optional MSC­based strategy for treating AS.


Assuntos
Aterosclerose/terapia , Células-Tronco Pluripotentes Induzidas/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Animais , Aterosclerose/sangue , Aterosclerose/complicações , Aterosclerose/imunologia , Células Cultivadas , Citocinas/sangue , Citocinas/imunologia , Humanos , Células-Tronco Pluripotentes Induzidas/imunologia , Inflamação/sangue , Inflamação/complicações , Inflamação/imunologia , Inflamação/terapia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/imunologia , Camundongos , Camundongos Endogâmicos C57BL
13.
Eur J Clin Pharmacol ; 72(11): 1327-1334, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27488389

RESUMO

PURPOSE: The aim of this study was to investigate whether any of the single-nucleotide polymorphisms (SNPs) in the POR gene were significantly associated with CYP activity and expression, and could contribute to the total variability in stable warfarin maintenance doses in Han Chinese. METHODS: A total of 408 patients treated at the First Affiliated Hospital of Sun Yat-Sen University were eligible for the study and had attained a stable warfarin maintenance dose at the start of the investigation. Demographics, warfarin maintenance doses, and concomitant medications were documented. Genomic DNA was extracted from peripheral blood samples and genotyped for ten SNPs (CYP 2C9*2 and *3, CYP4F2 rs2108622, VKORC1 -1639C>T, and potential POR genes of rs10239977, rs3815455, rs41301394, rs56256515, rs1057868, and rs2286823) using the Sequenom MassARRAY genotyping system. RESULTS: A predictive model of warfarin maintenance dose was established and indicated that age, gender, body surface area, aspirin use, CYP2C9*3, CYP4F2 rs2108622, VKORC1 -1639C>T, and POR*37 831-35C>T accounted for 42.4 % of dose variance in patients undergoing anticoagulant treatment. The contribution of POR*37 831-35C>T to warfarin dose variation was only 3.9 %. CONCLUSIONS: For the first time, the SNP POR*37 831-35C>T was confirmed as a minor but statistically significant factor associated with interindividual variation in warfarin maintenance dose in Han Chinese. The POR*37 gene polymorphism should be considered in future algorithms for faster and more reliable achievement of stable warfarin maintenance doses.


Assuntos
Anticoagulantes/administração & dosagem , Grupo com Ancestrais do Continente Asiático/genética , Sistema Enzimático do Citocromo P-450/genética , Modelos Biológicos , Varfarina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Varfarina/uso terapêutico , Adulto Jovem
14.
Oncol Rep ; 35(6): 3714-20, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27108782

RESUMO

Hydrogen sulfide (H2S) participates in diverse physiological and pathophysiologic processes of cancer both in vitro and in vivo. We have previously reported the proliferation/anti-apoptosis/angiogenesis/migration effects of exogenous H2S on liver cancer and glioma via amplifying the activation of NF-κB and p38 MAPK/ERK1/2-COX-2 pathway. However, the effects of H2S on EC109 esophageal cells remain unclear. The present study demonstrated the effects of exogenous H2S on cancer cell growth via activating HSP90 pathways in EC109 esophageal cells. EC109 esophageal cells were treated with 400 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of HSP90, bcl-2, caspase-3, bax and MMP-2 were detected by western blot assay. Cell viability was detected by Cell Counting Kit-8 (CCK-8). The migration rate was analyzed using a Transwell migration assay and ImageJ software. NaHS promoted cell proliferation, as evidenced by an increase in cell viability. In addition, NaHS treatment reduced apoptosis, as indicated by the increased bcl-2 expression and decreased cleaved caspase-3 and bax expression. Importantly, exposure of NaHS increased the expression of MMP-2, the migration rate and expression of VEGF. Notably, co-treatment of EC109 cells with NaHS and GA (an inhibitor of HSP90 pathway) largely suppressed the aforementioned NaHS-induced effects. The findings of the present study provided novel evidence that HSP90 pathway was involved in NaHS-induced cancer cell proliferation, anti-apoptosis, angiopoiesis and migration in EC109 esophageal cells.


Assuntos
Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/patologia , Proteínas de Choque Térmico HSP90/metabolismo , Sulfeto de Hidrogênio/farmacologia , Neovascularização Patológica/tratamento farmacológico , Caspase 3/biossíntese , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Humanos , Metaloproteinase 2 da Matriz/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Sulfetos/farmacologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Proteína X Associada a bcl-2/biossíntese
15.
Stroke ; 46(1): 157-63, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25424480

RESUMO

BACKGROUND AND PURPOSE: Chronic kidney disease may increase the risk for ischemic stroke or systemic embolism in patients with nonvalular atrial fibrillation (AF). We conducted a meta-analysis to summarize all published studies to investigate the link between chronic kidney disease and risk of thromboembolic events in AF. METHODS: We performed a literature search using MEDLINE (source PubMed, 1966 to July, 2014) and EMBASE (1980 to July 2014) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. RESULTS: Eighteen studies involving 538 479 patients and 41 719 incident thromboembolic events were identified. From the pooled analysis, AF patients with estimated glomerular filtration rate <60 mL/min compared with those with estimated glomerular filtration rate ≥60 mL/min experienced a significantly increased risk for developing thromboembolic events (relative risk, 1.62 [95% confidence interval, 1.40-1.87; P<0.001]). The annual rate of thromboembolic events increased by 0.41% (95% confidence interval, 0.17%-0.65%) for a 10 mL/min decrease in renal function. Addition of renal impairment to CHADS2 slightly improved the stroke risk stratification. CONCLUSIONS: Impaired renal function is an independent predictor of stroke or systemic embolism in patients with nonvalvular AF. Consideration of renal function may improve stroke risk stratification in patients with AF.


Assuntos
Fibrilação Atrial/complicações , Insuficiência Renal Crônica/complicações , Acidente Vascular Cerebral/etiologia , Tromboembolia/etiologia , Taxa de Filtração Glomerular , Humanos , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença
16.
Cardiovasc Ther ; 30(3): 152-61, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21167013

RESUMO

AIMS: We evaluated effects of the nonpeptide angiotensin (ANG)-(1-7) analog AVE 0991 (AVE) on cardiac function and remodeling as well as transforming growth factor-beta1 (TGF-ß1)/tumor necrosis factor-alpha (TNF-α) expression in myocardial infarction rat models. METHODS AND RESULTS: Sprague-Dawley rats underwent either sham surgery or coronary ligation. They were divided into four groups: sham, control, AVE, and AVE+A-779 [[D-Ala(7) ]-ANG-(1-7), a selective antagonist for the ANG-(1-7)] group. After 4 weeks of treatment, the AVE group displayed a significant elevation in left ventricular fractional shorting (LVFS) (25.5 ± 7.3% vs. 18.4 ± 3.3%, P < 0.05) and left ventricular ejection fraction (LVEF) (44.8 ± 7.6% vs. 32.7 ± 6.5%, P < 0.05) when compared to the control group, but no effects on the left ventricular end-diastolic and end-systolic diameters (LVDd and LVDs, respectively) were observed. In addition, we found that the myocyte diameter (18 ± 2 µm vs. 22 ± 4 µm, P < 0.05), infarct size (42.6 ± 3.6% vs. 50.9 ± 4.4%, P < 0.001) and collagen volume fraction (CVF) (16.4 ± 2.2% vs. 25.3 ± 3.2%, P < 0.001) were significantly reduced in the AVE group when compared to the control group. There were no differences in LVFS, LVEF, myocyte diameter, and infarct size between the control and AVE+A-779 groups. AVE also markedly attenuated the increased mRNA expression of collagen I (P < 0.001) and collagen III (P < 0.001) and inhibited the overexpression of TGF-ß1 (P < 0.05) and TNF-α (P < 0.05) compared to the control group. CONCLUSION: AVE could improve cardiac function and attenuate ventricular remodeling in MI rat models. It may involve the inhibition of inflammatory factors TGF-ß1/TNF-α overexpression and the action on the specific receptor Mas of ANG-(1-7).


Assuntos
Cardiotônicos/farmacologia , Imidazóis/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/patologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Angiotensina II/análogos & derivados , Angiotensina II/farmacologia , Animais , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Cardiomegalia/prevenção & controle , Colágeno/genética , Colágeno/metabolismo , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Masculino , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Fragmentos de Peptídeos/farmacologia , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas-G/efeitos dos fármacos , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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