RESUMO
Background: Epicardial adipose tissue (EAT) acts as an active immune organ and plays a critical role in the pathogenesis of heart failure (HF). However, the characteristics of immune cells in EAT of HF patients have rarely been elucidated. Methods: To identify key immune cells in EAT, an integrated bioinformatics analysis was performed on public datasets. EAT samples with paired subcutaneous adipose tissue (SAT), heart, and peripheral blood samples from HF patients were collected in validation experiments. T cell receptor (TCR) repertoire was assessed by high-throughput sequencing. The phenotypic characteristics and key effector molecules of T lymphocytes in EAT were assessed by flow cytometry and histological staining. Results: Compared with SAT, EAT was enriched for immune activation-related genes and T lymphocytes. Compared with EAT from the controls, activation of T lymphocytes was more pronounced in EAT from HF patients. T lymphocytes in EAT of HF patients were enriched by highly expanded clonotypes and had greater TCR clonotype sharing with cardiac tissue relative to SAT. Experiments confirmed the abundance of IFN-γ+ effector memory T lymphocytes (TEM) in EAT of HF patients. CCL5 and GZMK were confirmed to be associated with T lymphocytes in EAT of HF patients. Conclusion: EAT of HF patients was characterized by pronounced immune activation of clonally expanded IFN-γ+ TEM and a generally higher degree of TCR clonotypes sharing with paired cardiac tissue.
Assuntos
Tecido Adiposo , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/patologia , Gordura Subcutânea , Pericárdio/patologia , Receptores de Antígenos de Linfócitos TRESUMO
In late December 2019, COVID-19 was firstly recognized in Wuhan, China and spread rapidly to all of the provinces of China. The West Campus of Wuhan Union Hospital, the designated hospital to admit and treat the severe and critically ill COVID-19 cases, has treated a large number of such patients with great success and obtained lots of valuable experiences based on the Chinese guideline (V7.0). To standardize and share the treatment procedures of severe and critically ill cases, Wuhan Union Hospital has established a working group and formulated an operational recommendation, including the monitoring, early warning indicators, and several treatment principles for severe and critically ill cases. The treatment experiences may provide some constructive suggestions for treating the severe and critically ill COVID-19 cases all over the world.
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Betacoronavirus , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , COVID-19 , Teste para COVID-19 , China/epidemiologia , Técnicas de Laboratório Clínico , Terapia Combinada , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Estado Terminal , Dexametasona/uso terapêutico , Hospitais , Humanos , Imunização Passiva , Medicina Tradicional Chinesa , Pandemias , Pneumonia Viral/epidemiologia , Terapia Respiratória/métodos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Soroterapia para COVID-19Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/mortalidade , Hospitalização/tendências , Pneumonia Viral/sangue , Pneumonia Viral/mortalidade , Troponina I/sangue , Idoso , Biomarcadores/sangue , COVID-19 , Infecções por Coronavirus/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Pandemias , Pneumonia Viral/diagnóstico , Valor Preditivo dos Testes , SARS-CoV-2RESUMO
Paracaesicola n. gen., is erected herein to accommodate a new microcotylid species, Paracaesicola nanshaensis n. sp., collected from the Yongshu Reef, South China Sea. This species is the first monogenean to be recorded from the gills of Paracaesio sordida. The new species is characterized by the following features: (i) haptor short, with clamps arranged in two equal bilateral rows; (ii) testes numerous, arranged in two roughly alternating longitudinal rows, extending into the haptor; (iii) genital atrium armed with 16 robust spines, which are vertically arranged on top of the sausage shaped muscular male copulatory organ; and (iv) single vagina, bottle-shaped, with a distinctly bulbous vaginal atrium. The terminals of the reproductive system discriminate Paracaesicola n. gen. from all other genera in the Microcotylidae. Molecular phylogenetic analyses, based on partial 28S rDNA, places Paracaesicola nanshaensis n. sp. within the microcotylid clade, but its sequence differs from all known available microcotylid sequences.
TITLE: Paracaesicola nanshaensis n. gen., n. sp. (Monogenea, Microcotylidae), parasite branchial de Paracaesio sordida (Teleostei, Lutjanidae) de la mer de Chine méridionale. ABSTRACT: Paracaesicola n. gen. est érigé ici pour accueillir une nouvelle espèce de Microcotylidae, Paracaesicola nanshaensis n. sp., collectée sur le récif de Yongshu, mer de Chine méridionale. Cette espèce est le premier monogène signalé des branchies de Paracaesio sordida. La nouvelle espèce est caractérisée par : (i) hapteur court, avec des pinces disposées en deux rangées bilatérales égales ; (ii) testicules nombreux, disposés en deux rangées longitudinales à peu près alternées, s'étendant jusqu'au hapteur ; (iii) atrium génital armé de 16 épines robustes, disposées verticalement au-dessus de l'organe copulateur mâle, musculaire et en forme de saucisse ; et (iv) vagin unique, en forme de bouteille, avec un atrium vaginal nettement bulbeux. Les parties terminales du système reproducteur distinguent Paracaesicola n. gen. de tous les autres genres de Microcotylidae. Les analyses phylogénétiques moléculaires, basées sur l'ADNr 28S partiel, placent Paracaesicola nanshaensis n. sp. au sein du clade des Microcotylidae, mais sa séquence diffère de toutes les séquences de Microcotylidae disponibles.
Assuntos
Peixes/parasitologia , Brânquias/parasitologia , Filogenia , Trematódeos/anatomia & histologia , Trematódeos/classificação , Animais , China , Feminino , Doenças dos Peixes/parasitologia , Genitália Feminina/anatomia & histologia , Genitália Masculina/anatomia & histologia , Masculino , Oceanos e Mares , Especificidade da Espécie , Trematódeos/isolamento & purificaçãoRESUMO
BACKGROUND: Small dense low density lipoprotein-cholesterol (sdLDL-C), cholesterol ratios and carotid-femoral pulse wave velocity (cf-PWV) impart risk for all-cause morbidity and mortality independently of conventional cardiovascular disease (CVD) risk factors. This study was designed to identify feasible indicators for predicting arterial stiffness progression. METHODS: We followed up 816 normotensive participants without diabetes or CVD for nearly 5.0 years. Cholesterol parameters, ratios and other clinical and laboratory data were collected at baseline. cf-PWV were measured at baseline and the end of follow-up. RESULTS: PWV progression subjects had higher levels of PWV parameters, sdLDL-C and TG/HDL-C ratio. sdLDL-C and TG/HDL-C were significantly correlated with all PWV parameters. Multiple regression models showed that sdLDL-C was closely associated with follow-up PWV (ß = 0.222, p < 0.001) and â³PWV (ß = 0.275, p < 0.001). TG/HDL-C was only one cholesterol ratios that associated with all PWV parameters. sdLDL-C (OR = 2.070, 95%CI: 1.162 to 3.688, p = 0.014) and TG/HDL-C (OR = 1.355, 95%CI: 1.136 to 1.617, p = 0.001) could significantly determine the progression of PWV after correction for covariates. High sd-LDL-C quantiles subjects were more likely to develop arterial stiffness progression than low quantiles (Tertiles 3 vs Tertiles1, RR = 2.867, 95%CI: 1.106 to 7.434, p = 0.03). CONCLUSION: We founded that sdLDL-C and TG/HDL-C ratio can independently predict arterial stiffness progression in normotensive subjects, and high level sdLDL-C and TG/HDL-C ratio were associated with a higher risk of arterial stiffness.
Assuntos
Doenças Cardiovasculares/sangue , LDL-Colesterol/sangue , Colesterol/sangue , Rigidez Vascular , Adulto , Doenças Cardiovasculares/fisiopatologia , Artérias Carótidas/fisiopatologia , HDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de Risco , Triglicerídeos/sangueRESUMO
Arterial stiffness is an independent indicator of cardiovascular risk. Autoantibodies (AAs) against angiotensin AT1 receptor (AT1-AAs) and α1-adrenergic receptor (α1-AAs) are important in the pathogenesis of hypertension. We identified the types of AT1-AAs and α1-AAs in normotensive subjects, with the aim of determining whether these antibodies predict aortic stiffness progression. Carotid-femoral pulse wave velocity (cf-PWV) was used to measure aortic stiffness. Overall, 816 subjects (71% of those invited) underwent a medical examination and evaluation of aortic stiffness. The types of AT1-AAs and α1-AAs were measured at baseline. Meanwhile, plasma renin, angiotensin II (Ang II), and norepinephrine (NE) concentrations were measured at baseline and follow-up. Baseline mean cf-PWV was 9.90 ± 0.84 m/s and follow-up was 10.51 ± 1.12 m/s. The annualized ΔPWV was 0.12 ± 0.08 m/s/year. At the end of follow-up, 129 normotensive subjects developed hypertension and 144 subjects had PWV progression. After adjustment for covariates, AA type was independently associated with ΔPWV, annualized ΔPWV, and abnormal PWV. In our study, the risk of developing hypertension (RR =2.028, 95% CI: 1.227-3.351, P=0.006) and PWV progression (RR =2.910, 95% CI: 1.612-5.253, P<0.001) in AA-positive subjects was significantly higher than that in AA-negative subjects. Receiver operating characteristic (ROC) curve showed AA had an identify power to discriminate subjects with or without PWV and hypertension progression. We have shown for the first time that the types of A1-AAs and α1-AAs are independent predictors for aortic stiffness progression in normotensive subjects. Our data collectively support the utility of these AAs as potential markers of aortic stiffness.
Assuntos
Autoanticorpos/sangue , Hipertensão/imunologia , Receptor Tipo 1 de Angiotensina/imunologia , Receptores Adrenérgicos alfa 1/imunologia , Rigidez Vascular , Adulto , Área Sob a Curva , Biomarcadores/sangue , Feminino , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de Onda de Pulso , Curva ROC , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: High-sensitivity cardiac troponin is the most specific and sensitive biomarker of myocardial injury. However, no study has investigated whether the early concentration of high-sensitivity cardiac troponin is increased or is of value in predicting short-term prognosis in patients with type-A acute aortic dissection (AAD) in the emergency department. AIMS: To measure the high-sensitivity cardiac troponin T (hs-TnT) concentration in patients with type-A AAD upon hospital admission, and to assess its value in predicting short-term prognosis. METHODS: We enrolled consecutive patients with type-A AAD. Blood samples were collected on admission; hs-TnT concentrations were measured on the Elecsys 2010 system. High-sensitivity C-reactive protein (hs-CRP), D-dimer and other biochemical indicators were measured. Patients were divided into two groups according to hs-TnT concentration on admission (< or ≥0.014ng/mL). RESULTS: More than half (61.2%) of the 103 included patients had an hs-TnT concentration ≥0.014ng/mL. hs-TnT concentrations were significantly higher in those who died compared with survivors (0.292±0.516 vs. 0.069±0.154ng/mL; P=0.003). Multivariable Cox regression analysis suggested that hs-TnT is an independent factor for predicting in-hospital mortality risk (odds ratio: 2.202, 95% confidence interval: 1.111-4.367; P=0.024). Kaplan-Meier curves revealed a significant increase in hospital mortality in the hs-TnT(+) group compared with the hs-TnT(-) group (P=0.021). When hs-TnT was ≥0.042ng/mL, the sensitivity and specificity in predicting hospital short-term mortality were 70.8% and 76.4%, respectively. CONCLUSIONS: Our study suggests that hs-TnT concentration could be used as an early biomarker for the risk stratification of patients with type-A AAD in the emergency department; the relationship between hs-TnT concentration and long-term prognosis needs further investigation.
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Aneurisma Aórtico/sangue , Dissecção Aórtica/sangue , Biomarcadores/sangue , Troponina T/sangue , Doença Aguda , Adulto , Idoso , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/mortalidade , Aneurisma Aórtico/diagnóstico , Aneurisma Aórtico/mortalidade , Distribuição de Qui-Quadrado , China , Serviço Hospitalar de Emergência , Feminino , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) is a critical regulator for cellular oxygen balance. Myocardial hypoxia can induce the increased expression of HIF-1α. Our goals were to evaluate the value of HIF-1α in predicting death of patients with acute decompensated heart failure (ADHF) and describe the in vivo relationship between serum HIF-1α and N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels. METHOD: We included 296 patients who were consecutively admitted to the emergency department for ADHF. The primary end point was in-hospital death. The patients were categorized as HFrEF (patients with reduced systolic function) and HFpEF (patients with preserved systolic function) groups. RESULTS: In our patients, the median admission HIF-1α level was 2.95 ± 0.85 ng/ml. The HIF-1α level was elevated significantly in HFrEF patients and deceased patients compared with HFpEF patients and patients who survived. The HIF-1α level was positively correlated with NT-proBNP and cardiac troponin T levels, and negatively correlated with left ventricular ejection fraction and systolic blood pressure. Kaplan-Meier curves revealed a significant increase in in-hospital mortality in ADHF patients with higher HIF-1α levels. Multivariable Cox regression analysis showed that HIF-1α levels were not correlated with the short-term prognosis of ADHF patients. CONCLUSIONS: This is the first study to evaluate the circulating levels of HIF-1α in ADHF patients. Serum HIF-1α levels may reflect a serious state in patients with ADHF. Due to the limitations of the study, serum HIF-1α levels were not correlated with the in-hospital mortality based on regression analysis. Further studies are needed to demonstrate the diagnostic and/or prognostic role of HIF-1α as a risk biomarker in patients with ADHF.
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Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Mortalidade Hospitalar/tendências , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Admissão do Paciente/tendências , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND & OBJECTIVES: a0 ngiotensin II receptor type 1 (AT1) is known to be involved in the pathogenesis of hypertension. t0 his study was undertaken to explore the effect of active immunization against AT1 receptor on blood pressure and small artery remodelling in spontaneously hypertensive rat (SHR). METHODS: Male SHR and Wistar rats aged two months were actively immunized with different peptides (ATR12185ͱͲATR10014 and ATR12181) corresponding to particular sequences of rat AT1 receptor, while another SHR group was given losartan (10 mg/kg/day) orally once a day. Anti-AT1 receptor antibodies were detected by ELISA and blood pressure was measured. The effect of the antibodies on the artery and vascular smooth muscle cells (VSMCs) proliferation was studied. RESULTS: all immunized animals produced antibodies against the particular peptides. The systolic blood pressure was decreased in the SHR immunized with peptide-ATR12181 compared with the control. However, no changes were observed in the SHR immunized with other two peptides. The Wistar rats immunized with the three peptides did not show any changes in blood pressure. The media/lumen area ratio of the mesenteric artery was reduced in SHR immunized with ATR12181 and similar to that of the SHR treated with losartan. The antibody from SHR immunized with ATR12181 had no effect on the proliferation of VSMC. But it could inhibit the proliferation caused by angiotensin II and its effect at the titre of 1:40 was similar to that of 1µmol/l losartan. INTERPRETATION & CONCLUSIONS: Our findings demonstrated that the antibody from SHR immunized with ATR12181 had the effect of reducing blood pressure and target organ protection similar to losartan. Active immunization against AT1 receptor may be a promising strategy in future for the treatment of hypertension.
Assuntos
Hipertensão/fisiopatologia , Receptor Tipo 1 de Angiotensina/imunologia , Vacinação/métodos , Remodelação Vascular/fisiologia , Análise de Variância , Animais , Anticorpos/sangue , Determinação da Pressão Arterial , Ensaio de Imunoadsorção Enzimática , Hipertensão/imunologia , Losartan/farmacologia , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , Miócitos de Músculo Liso/imunologia , Miócitos de Músculo Liso/fisiologia , Peptídeos/imunologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Remodelação Vascular/imunologiaRESUMO
OBJECTIVE: To observe serum uric acid (UA) level distribution and explore risk factors of hyperuricemia (HUA) in a large cohort of active and retired employees underwent physical examination. METHODS: Physical examination was arranged for 21 700 active and retired employees from May 2010 to September 2011, 16 416 employees were examined and complete examination data were obtained in 14 044 subjects. The distribution characteristics of UA level and correlations of UA level and HUA prevalence rate with gender, age, body mass index (BMI), systolic pressure (SBP), diastolic pressure (DBP), fasting blood-glucose (FPG), serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were analyzed. RESULTS: HUA prevalence rate was 11.2% in this cohort, which was significantly higher in males (15.8%) than in females (4.1%, P < 0.05). The UA level and the HUA prevalence rate presented a "J" curve relationship with aging and positively correlated with BMI, SBP, DBP, TG, LDL-C, TC and FPG while negatively correlated with HDL-C. Multiple linear regression analysis showed that SBP, BMI, FPG, TG, and LDL-C were independent risk factors while HDL-C and female gender were the protective factors of HUA(all P < 0.01). Aging and high DBP were independent risk factors of HUA for females (all P < 0.05) and LDL-C was risk factor of HUA for males (P < 0.05). CONCLUSIONS: Serum UA level presents a "J" wave relationship with aging. The risk factors of HUA are increased SBP, BMI, FPG, TG, LDL-C while the protective factors of HUA are female gender and high HDL-C.
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Hiperuricemia/epidemiologia , Ácido Úrico/sangue , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Físico , Prevalência , Fatores de RiscoRESUMO
The published antibodies (Abs) against CD22 on B cells including Epratuzumab could inhibit B cell activation mainly through binding to C2-set Ig domain of CD22, but they are rarely reported to modulate the pathogenic CD4(+) T cell function in systemic lupus erythematosus (SLE). Recently, it was proved that the extracellular amino-terminal V-set Ig domain of CD22 might mediate the interaction of B and T cells, but for now the exact effect of this domain on CD4(+) T cell biology have not been identified. Thus, in this study, we screened out a peptide termed B2285 from this V-set Ig domain, developed the novel specific anti-B2285 Abs in rabbits, and investigated their effects in MRL/lpr mice with spontaneous SLE. The results showed that anti-B2285 Abs could ameliorate the disease severity obviously in spontaneous SLE mice with the decreased differentiations of Th1 and Th17 cells and no changes of Th2 and Treg cells. In co-cultured B cells and CD4(+) T cells, this specific anti-CD22 Abs was observed to inhibit the anti-dsDNA Abs production, CD4(+) T cells proliferation, the protein levels of T-bet and RORγt, and the mRNA levels of TNF-α, IFN-γ, IL-6 and IL-17 in CD4(+) T cells. Moreover, the expression of CD45RO on CD4(+) T cells could be also apparently diminished by this novel Abs. The data suggested that anti-B2285 Abs could slow SLE progression significantly by regulating Th1 and Th17 cells function via B-T cell interaction and the cytokine network regulation. The treatment against V-set Ig domain of CD22 would be a valuable therapeutic method for SLE and other autoimmune diseases.
Assuntos
Epitopos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Linfócitos B/imunologia , Linfócitos B/patologia , Comunicação Celular , Diferenciação Celular/imunologia , Separação Celular , Feminino , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos MRL lpr , Peptídeos/química , Peptídeos/imunologia , Estrutura Terciária de Proteína , Coelhos , Índice de Gravidade de Doença , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/química , Células Th1/patologia , Células Th17/patologiaRESUMO
In this study, we investigated the hypothesis that regulatory T cells (T(reg)) are involved in the immunomodulatory effects of statins on rheumatoid arthritis (RA) patients. The 12-week study cohort consisted of 55 RA patients and 42 control subjects allocated to either a group treated with atorvastatin (AT) (20 mg/day) or a non-AT group. T(reg) numbers, suppressive function, serum inflammatory markers, and disease activity were evaluated before and after the therapy. Furthermore, the effects of AT on the frequency and suppressive function of T(reg) were determined in vitro. Our data revealed that the suppressive function of T(reg) from RA patients significantly decreased compared with that of control subjects. AT significantly reduced erythrosedimentation, C-reactive protein, and disease activity. Concomitantly, T(reg) numbers and suppressive functions were significantly improved by AT. Consistent with the in vivo experiments, AT promoted the generation of T(reg) from primary T cells and enhanced preexisting T(reg) function in vitro. Moreover, we showed that PI3K-Akt-mTOR and ERK signal pathways were involved in the induction of T(reg) by AT. In conclusion, AT significantly increased T(reg) numbers and restored their suppressive function in the RA patients, and this may be relevant in the modulation of uncontrolled inflammation in this disorder.
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Anticolesterolemiantes/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Ácidos Heptanoicos/uso terapêutico , Pirróis/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Adulto , Atorvastatina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Anti-angiotensin II receptor subtype 1 (AT1 receptor) autoantibodies have previously been shown in sera of hypertensive patients. This study assessed whether anti-AT1-receptor autoantibody in serum is correlated with the efficacy of an AT1-receptor blocker (ARB; candesartan)-based regimen in hypertensive patients after 8 weeks of treatment. DESIGN: The Study of Optimal Treatment in Hypertensive Patients with Anti-AT1-Receptor Autoantibodies is a multicentre, randomised, blinded endpoint, open-label, parallel-group comparison clinical trial conducted in five centres in Wuhan, China. Treatment is designed as stepwise added-on therapy to reduce blood pressure (BP) < 140/90 mm Hg. 512 patients with moderate to severe primary hypertension were randomly assigned to an 8-week treatment with either ARB (candesartan)-based regimen (n=257) or ACE inhibitor (imidapril)-based regimen (n=255). RESULTS: Systolic and diastolic BP was reduced significantly in both treatment groups. The candesartan-based regimen achieved a significantly greater systolic BP reduction than imdapril (30.8 ± 10.3 vs 28.8 ± 10.3 mm Hg, p = 0.023). In those anti-AT1 receptor autoantibody-positive hypertensive patients, the mean systolic BP at baseline was higher than in the anti-AT1 receptor autoantibody-negative group (160.5 ± 16.5 vs 156.2 ± 17.7 mm Hg; p = 0.006). The mean BP reduction was greater in the candesartan-based regimen than the imidapril-based regimen (-35.4 ± 9.8/16.9 ± 6.9 vs -29.4 ± 9.8/14.2 ± 6.9 mm Hg; p = 0.000 and 0.002, respectively), and more patients on imidapril required add-on medications to achieve BP control (94% vs 86%; p=0.03). No correlation was observed between the titre of anti-AT1 receptor autoantibody and the efficacy of candesartan-based therapy. In those anti-AT1 receptor autoantibody-negative patients similar BP lowering was reached in the candesartan and the imidapril-based regimens. CONCLUSIONS: An ARB-based regimen is more effective in BP lowering than an ACE inhibitor-based regimen in the presence of anti-AT1 receptor autoantibodies. Trial registration number This trial has been registered at http://www.register.clinicaltrials.gov/ (identifier: NCT00360763).
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Anti-Hipertensivos/uso terapêutico , Autoanticorpos/sangue , Benzimidazóis/uso terapêutico , Hipertensão/tratamento farmacológico , Imidazolidinas/uso terapêutico , Receptor Tipo 1 de Angiotensina/imunologia , Tetrazóis/uso terapêutico , Adulto , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Benzimidazóis/efeitos adversos , Compostos de Bifenilo , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Hipertensão/imunologia , Hipertensão/fisiopatologia , Imidazolidinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tetrazóis/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: To observe the positive rates of autoantibodies against beta1 adrenergic receptors (beta1-receptor) and angiotensin II type 1 receptors (AT(1)-receptor) in type 2 diabetes patients with or without hypertension. METHODS: The epitopes of the second extracellular loop of beta1-receptor (197 - 222) and AT(1) receptor (165 - 191) were synthesized and serum autoantibodies were determined in type 2 diabetes patients with hypertension (n = 171) or without hypertension (n = 106). Left ventricular dimension was determined by echocardiography. The 24-hour urinary protein was measured by ELISA. The risk factors for enlarged left ventricle were analyzed by multiple logistic regressions. RESULTS: The positive rates of the autoantibodies against beta1-receptors (45.0%) and AT(1)-receptor (46.2%) in patients with type 2 diabetes with hypertension were significantly higher than those in patients with type 2 diabetes without hypertension (16.0% and 10.4%, respectively, all P < 0.01). In type 2 diabetes patients with hypertension and enlarged left ventricle, the positive rates of the autoantibodies against beta1-receptor 61.4% (35/57) and against AT(1)-receptor 64.9% (37/57)were significantly higher than those in type 2 diabetes patients with normal left ventricular dimension (36.8%, 42/114 and 36.8%, 42/114, respectively, all P < 0.01). Regression analysis demonstrated that course of disease, systolic pressure, serum autoantibodies against beta1 adrenergic receptor and angiotensin II type 1 receptors sera autoantibodies were independent risk factors for left ventricular enlargement (all P < 0.05). CONCLUSION: The serum beta1 and AT(1)-receptor autoantibodies are related to enlarged left ventricle in type 2 diabetes patients with hypertension and suggest that autoantibodies against beta1 and AT(1)-receptor might play important roles in the pathogenesis of type 2 diabetes patients with hypertension and enlarged left ventricle.
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Autoanticorpos/sangue , Diabetes Mellitus Tipo 2/imunologia , Hipertrofia Ventricular Esquerda/imunologia , Idoso , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertrofia Ventricular Esquerda/complicações , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina/imunologia , Receptores Adrenérgicos beta 1/imunologiaRESUMO
AIMS: Increasing evidences confirm the role of immune activation in the pathogenesis of chronic heart failure (CHF). Regulatory T cells appear central to the control of immune homeostasis. We assessed the hypothesis that the circulating frequency and function of CD4+CD25+ Foxp3+CD127(low) T regulatory cells (Tregs) would be deranged in patients with CHF. METHODS: Ninety-nine CHF patients due to non-ischemic (NIHF) or ischemic etiology (IHF) and 24 control donors were enrolled in the study. Frequency of circulating Tregs was evaluated by flow cytometry. Foxp3 in peripheral blood mononuclear cells (PBMCs) was assayed at the mRNA level by real-time PCR. Functional properties of Tregs to suppress proliferation and pro-inflammatory cytokines secretion of activated CD4+CD25(-) T cells were measured by proliferation assay and ELISA. RESULTS: The results demonstrated that CHF patients had significantly lower frequency of circulating Tregs and reduced Foxp3 expression in PBMCs compared with control donors. Moreover, Tregs from CHF patients showed compromised function to suppress CD4+CD25(-) T cells proliferation and pro-inflammatory cytokines secretion. A similar pattern with reduced Tregs frequency and compromised function was found in both NIHF and IHF patients. Correlation analysis suggested that Tregs frequency and function positively correlated with LVEF, whereas negatively correlated with LVEDD and NT-proBNP in patients with CHF. CONCLUSIONS: Our data are the first to demonstrate that frequencies of circulating Tregs in patients with CHF are reduced and their suppressive function compromised independently of the etiology. Defective Tregs may be an underlying mechanism of immune activation in CHF patients.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Insuficiência Cardíaca/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Subunidade alfa de Receptor de Interleucina-7/metabolismo , Linfócitos T Reguladores/imunologia , Adulto , Doença Crônica , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Atherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Recently, CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells and Th17 cells have been described as two distinct subsets and have the opposite effects on autoimmunity. Clinical observation has revealed that the Th17/Treg imbalance exists in patients with acute coronary syndrome. We investigated whether the Th17/Treg functional imbalance existed during atherogenesis in ApoE(-/-) mice. METHODS AND RESULTS: Th17/Treg functions at different levels including cell frequencies, related cytokine secretion and key transcription factors were investigated comparatively between ApoE(-/-) mice and their age-matched C57BL/6J mice. The results demonstrated that ApoE(-/-) mice revealed significantly increased secretion of Th17 related cytokines (IL-17 and IL-6) and expression of transcription factor (RORgammat) levels and obviously decreased number in Treg cells, secretion of Treg related cytokines (TGF-beta(1)) and expression of transcription factor (Foxp3) levels as compared with age-matched C57BL/6J mice. Th17 related mediators reached their maximum expression values at the early stage (8-16weeks of age) in ApoE(-/-) mice, and then followed by continuous depression of their expression levels. Meanwhile, the expression of Treg related mediators was much lower in ApoE(-/-) mice than in their age-matched wild-type littermates. CONCLUSIONS: Th17/Treg functional imbalance exists during atherogenesis in ApoE(-/-) mice, suggesting a potential role of Th17/Treg imbalance in the formation and progression of atherosclerosis.
Assuntos
Apolipoproteínas E/imunologia , Aterosclerose/metabolismo , Interleucina-17/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Animais , Aorta/patologia , Apolipoproteínas E/genética , Aterosclerose/imunologia , Aterosclerose/patologia , Citocinas/genética , Citocinas/imunologia , Humanos , Interleucina-17/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Subpopulações de Linfócitos T/citologia , Linfócitos T Reguladores/citologia , Células Th1/citologiaRESUMO
OBJECTIVE: To explore the relation between the positive rates of autoantibodies against beta(1) adrenergic receptor (beta1-receptor)and (M2-receptor) with urinary albumin excretion rate (UAER) in type 2 diabetes patients with refractory hypertension. METHODS: Autoantibodies against beta(1)- and M(2)-receptor as well as autoantibodies were determined in type 2 diabetes patients with (n = 136) or without (n = 111) refractory hypertension, hypertensive patients without renal failure (n = 60) and healthy control subjects (n = 40, control) by ELISA. RESULTS: The positive rates of the autoantibodies against beta1-receptors (44.9%) and M(2)-receptor (37.5%) in patients with type 2 diabetes with refractory hypertension were significantly higher than those in patients with type 2 diabetes without refractory hypertension (27.9% and 24.3%, respectively, all P < 0.05), in patients with hypertension without renal failure (11.7% and 15.0%, all P < 0.01) and in healthy controls (8.3% and 7.5%, all P < 0.01). In type 2 diabetes patients with refractory hypertension and renal failure (UAER > or = 200 microg/min), the positive rates of the autoantibodies against beta(1)-receptor (87.1%, 27/31) and against M(2)-receptor (67.7%, 21/31) were significantly higher than those in type 2 diabetes patients with refractory hypertension but without renal failure (UAER 20 - 199 microg /min, 46.7%, 28/60 and 41.7%, 25/60, respectively, all P < 0.05). CONCLUSION: The serum beta(1)- and M (2)-receptor autoantibodies are positively associated with the UAER level and suggest that these autoantibodies against beta(1) and M(2)-receptor may play important roles in the pathogenesis of the type 2 diabetes with refractory hypertension.
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Albuminúria/etiologia , Autoanticorpos/análise , Diabetes Mellitus Tipo 2/imunologia , Hipertensão/imunologia , Idoso , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Receptor Muscarínico M2/imunologia , Receptores Adrenérgicos beta 1/imunologiaRESUMO
BACKGROUND: Recently, it has been proposed that the autoantibodies against various cardiovascular receptors play a role in the pathogenesis of primary hypertension. In this study, we aimed to identify whether or not there are autoantibodies against cardiovascular L-type Ca2+ channels in patients with primary hypertension. METHODS: A peptide corresponding to the sequence 2-16 of the alpha1c-subunit of L-type Ca2+ channel was used as an antigen to screen the autoantibodies from 90 patients with primary hypertension and 45 healthy controls by an enzyme-linked immunosorbent assay (ELISA). The clinical data of 90 hypertensive patients were compared between patients with and without these autoantibodies. RESULTS: Serum from 3 (6.7%) of the 45 healthy controls, 33 (36.7%) of 90 hypertensives showed positive responses in ELISA (P < 0.01). The prevalence of such autoantibodies in two subgroups of hypertensives with coronary heart disease (9/21, 57.14%, P < 0.05) and left ventricular diastolic dysfunction (28/63, 44.4%, P < 0.05) was higher than in those without the corresponding complications. And the patients with such autoantibodies had lower E/A than patients without such autoantibodies (0.803 +/- 0.191 vs. 1.004 +/- 0.322, P = 0.002). CONCLUSION: There are autoantibodies against vascular L-type Ca2+ channels in patients with primary hypertension.
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Autoanticorpos/sangue , Canais de Cálcio Tipo L/imunologia , Hipertensão/imunologia , Adulto , Idoso , Sequência de Aminoácidos , Animais , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Ratos , Ratos Sprague-DawleyRESUMO
Agonistic AT(1) receptor autoantibodies (AT(1)-AAs) have been described in the patients with malignant hypertension or preeclampia. Furthermore, AT(1)-AAs were highly associated with refractory hypertension. Function of vascular smooth muscle cells (VSMCs) is important in the regulation of blood pressure. We investigated and compared the ability of angiotensin II (Ang II) and AT(1)-AAs to stimulate the intracellular calcium mobilization and cellular proliferation of rat VSMCs. Twenty-two patients with refractory hypertension, 24 patients with non-refractory hypertension and 37 normotensives were recruited. The serum of each patient was detected for the presence of AT(1)-AAs by ELISA. Ang II and the AT(1)-AAs from the sera of patients were used to stimulate rat VSMCs in vitro. AT(1)-AAs were detected in 10/22, 3/24 and 3/37 of patients with refractory hypertension, non-refractory hypertension and normotensives, respectively. AT(1)-AAs led the increase intracellular calcium mobilization in a dose-dependent manner and cellular proliferation of VSMCs just as Ang II. Both of these effects caused by AT(1)-AAs were blocked with losartan or a peptide corresponding to a part of the second extracellular loop of AT(1) receptor. Since AT(1)-AAs exhibited pharmacological activity in rat VSMCs just as Ang II, they might play a role in the elevation of peripheral vascular resistance and in vascular remodeling. And AT(1)-AAs were suggested to involve in resistance to antihypertensive therapy.
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Angiotensina II/metabolismo , Autoanticorpos/sangue , Cálcio/metabolismo , Hipertensão/metabolismo , Músculo Liso Vascular/metabolismo , Receptor Tipo 1 de Angiotensina/imunologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Proliferação de Células , Células Cultivadas , Relação Dose-Resposta Imunológica , Feminino , Humanos , Hipertensão/imunologia , Losartan/farmacologia , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/citologia , Músculo Liso Vascular/imunologia , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/agonistasRESUMO
OBJECTIVE: To investigate the effects of autoantibodies against alpha(-) adrenergic receptor on cardiac remodeling in patients with hypertension. METHODS: Five hundred and fifty three patients with hypertension in our hospital were selected. The autoantibodies against alpha(1) adrenergic receptor in sera of donor were detected by ELISA, and the results of echocardiography were recorded. By multiple logistic regressions, the risk factors were analyzed on left ventricular enlargement of hypertension. RESULTS: The percentage of autoantibodies against alpha(1) adrenergic receptor positive was 32.3% (179/553). There were significant difference between the positive group and negative group on the ratio of left atrial enlargement (53.6%, 44.3%, respectively; P < 0.05) and left ventricular enlargement (12.8%, 6.1%, respectively; P < 0.01). The result of regression analysis demonstrated that 4 risk factors were related to left ventricular enlargement, including male, course of disease, heart rate (HR) and autoantibodies against alpha(1) adrenergic receptor in the serum (all P < 0.05). CONCLUSIONS: The autoantibodies against alpha(1) adrenergic receptor have a relationship with left ventricular enlargement of hypertension. Patients with the activity of autoantibodies against alpha(1) adrenergic might contribute to predict cardiac remodeling.