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1.
ESC Heart Fail ; 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31400092

RESUMO

AIMS: This study aimed to evaluate the prognostic significance of nutritional status in post-discharge Asians with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We examined the prognostic implications of body mass index (BMI) and nutritional markers among consecutive patients hospitalized for HFpEF. Nutritional metrics were estimated by serum albumin (SA), prognostic nutritional index (PNI), Controlling Nutritional Status (CONUT) score, and geriatric nutritional risk index. Among 1120 patients (mean age: 77.2 ± 12.6 years, 39.4% men), mean SA levels, PNI, CONUT scores, and geriatric nutritional risk index were 3.3 ± 0.6 g/dL, 40.2 ± 8.7, 5.5 ± 2.1, and 95.9 ± 14.5, respectively. Lean body size, higher white blood cell counts and C-reactive protein levels, anaemia, and lack of angiotensin blocker use were independently associated with malnutrition (defined by SA < 3.5 g/dL). Higher SA levels [hazard ratio (HR): 0.67 (95% confidence interval, CI: 0.53-0.85)], higher PNI [HR: 0.97 (95% CI: 0.95-0.99)], and higher geriatric nutritional risk index [HR: 0.98 (95% CI: 0.97-0.99)] (all P < 0.05) were all associated with longer survival, with higher CONUT score [HR: 1.08 (95% CI: 1.02-1.13)] exhibited higher mortality in Cox regression models and with higher SA levels/PNI but not BMI further contributing to the reduced rate of re-hospitalization (both P < 0.05). Categorizing BMI (25 kg/m2 as cut-off) and nutritional status showed significantly higher mortality rates among patients with lower BMI/malnutrition than among those with BMI/better nutrition (SA level, PNI, and CONUT score, all P < 0.01). Restricted cubic spline regression revealed a marked survival benefit of better nutrition with increasing BMI (adjusted Pinteraction for both SA level and PNI: <0.001; adjusted Pinteraction for CONUT score: 0.046). CONCLUSIONS: Malnutrition was frequently and strongly associated with systemic inflammation in Asian patients hospitalized for acute HFpEF. Our findings also indicate that nutrition may play a pivotal role in metabolic protection in this population.

2.
ESC Heart Fail ; 6(4): 723-732, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30993903

RESUMO

AIMS: Left atrial (LA) remodelling is an important predictor of cardiovascular events of heart failure (HF) and atrial fibrillation. Data regarding diagnostic value of LA remodelling on diastolic dysfunction (DD) and preclinical HF remain largely unexplored. METHODS AND RESULTS: We assessed LA dimension (LAD) in 8368 consecutive asymptomatic Asians (mean age: 49.7, 38.9% women) and related such measure to updated American Society of Echocardiography (ASE) DD criteria and newly revised N-terminal pro-brain natriuretic peptide (NT-proBNP) cut-off (≥125 pg/mL) and HF with preserved ejection fraction criteria incorporating NT-proBNP and echocardiography parameters by the European Society of Cardiology (ESC). LAD and indexed LAD (LADi) were both inversely correlated with myocardial relaxation e' and positively associated with indexed LA volume, left ventricular E/e', and tricuspid regurgitation velocity (all P < 0.001) and showed significantly graded increase across ASE-defined 'normal', 'inconclusive', and 'DD' categories (30.9, 34.4, and 36.5 mm; 16.7, 19.1, and 20.6 mm/m2 , for LAD/LADi, both P for trend: <0.001, respectively). Substantial differences of LAD/LADi (31.3 vs. 33.6 mm/16.7 vs. 19.2 mm/m2 , both P < 0.001) between ESC low and high HF probability using NT-proBNP cut-off were also observed. Multivariate linear and logistic models demonstrated that LAD set at 34 mm was independently associated with ASE-defined diastolic indices, DD existence, and elevated NT-proBNP (all P < 0.05). The use of LAD further yielded high diagnostic accuracy in DD (area under receiving operative characteristic curve: 0.77, 95% confidence interval [0.73, 0.80]; negative predictive value: 97.9%) and in ESC-recommended HF with preserved ejection fraction criteria (area under receiving operative characteristic curve: 0.70, 95% confidence interval [0.65, 0.75]; negative predictive value: 98.7%) with high predictive value in LA remodelling (>34 mL/m2 ; positive predictive value: 96%) and well-discriminated ESC-recommended NT-proBNP (≥125 pg/mL, LAD: 37 mm) for HF. CONCLUSIONS: Single utilization of atrial remodelling is highly useful for ruling out presence of DD and provides practical threshold for identifying preclinical HF based on most updated guidelines.

4.
PLoS One ; 14(1): e0207089, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30608944

RESUMO

Thoracic aortic calcification (TAC) is tightly linked to pathological atherosclerosis and associated with certain cardiovascular diseases. While diabetes mellitus (DM) is known as a coronary heart disease equivalent, we examined the presence of TAC across the dysglycemic spectrum of diabetes mellitus (DM). We consecutively studied 3003 asymptomatic ethnic Asians underwent annual cardiovacular health survey, and further categorized them into: 1) 1760 normo-glycemic, 2) 968 pre-diabetic, and 3) 274 overt DM based on dysglycemic indices and medical histories. Several TAC parameters were assessed using non-contrast multi-detector computed tomography (MDCT), and related to dysglycemic indices or diabetes mellitus status. A remarkably graded increases of adjusted total TAC calcium burden, volume and density were seen across Non-diabetes, Pre-diabetes, and diabetes mellitus categories and positively correlated with all dysglycemic profiles (all p<0.001). Multi-variate logistic and linear regression models demonstrated independent associations between greater TAC density and all dysglycemic indices (Coef: 2.5, 1.4, 6.8 for fasting, postprandial sugar and HbA1c) and diabetes mellitus status (all p<0.05). Furthermore, Receiver-operating characteristic curves (ROC) showed fasting sugar and postprandial sugar set at 103mg/dL and 111mg/dL, separately, with HbA1c set at 5.8% all predict the presence of aortic calcification. Dysglycemic status, even without overt diabetes mellitus, were tighly linked to subclinical, pathological thoracic aortic calcification.


Assuntos
Aorta Torácica/patologia , Grupo com Ancestrais do Continente Asiático , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Complicações do Diabetes/epidemiologia , Calcificação Vascular/complicações , Calcificação Vascular/epidemiologia , Glicemia/metabolismo , Complicações do Diabetes/sangue , Complicações do Diabetes/fisiopatologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia
5.
PLoS One ; 13(11): e0207284, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30458019

RESUMO

Visceral adiposity is associated with cardiovascular disease, an association that may be mediated in part by inflammation. We hypothesized that regional measures of visceral adiposity would associate with commonly obtained clinical measures of immune status. We consecutively studied 3,291 subjects (mean age, 49.8±9.8 years) who underwent an annual cardiovascular risk survey. Peri-cardial (PCF) and thoracic peri-aortic adipose tissue (TAT) volumes were determined by dedicated computed tomography (CT) software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Hepatic steatosis was assessed by abdominal ultrasonography. We explored cross-sectional associations between visceral fat measures and high-sensitivity C-reactive protein (hs-CRP), leukocyte counts, and the neutrophil-to-lymphocyte ration (NLR). Among 3,291 study participants, we observed positive linear associations between PCF and TAT, higher degree of hepatic steatosis and hs-CRP, various leukocyte counts, either total and its differential counts, and NLR (all trend p<0.001). Multi-variate linear and logistic regression models showed independent associations between PCF/TAT (ß-Coef: 0.14/0.16, both p<0.05) and total WBC counts, with only TAT further demonstrated significant relations with neutrophil counts and NLR (both p<0.05) and independently identified abnormally high WBC and NLR (Odds ratio: 1.18 & 1.21, both p<0.05). C-statistics showed significant incremental model prediction for abnormally high WBC and NLR (both ΔAUROC<0.05) when TAT was superimposed on traditional cardiovascular risks and biochemical information. Greater visceral adiposity burden and hepatic steatosis may be associated with higher circulating leukocyte counts and markers for atherosclerosis, with more pronounced influences for peri-aortic adiposity. Our data suggested the differential biological impacts for region-specific visceral adiposity.

6.
J Clin Hypertens (Greenwich) ; 20(6): 1027-1035, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29749701

RESUMO

The authors consecutively assessed various arterial pulse-wave velocity (PWV) indices and ankle-brachial index (ABI) by an automatic device (VP2000, OMRON Health Care Co. Ltd., Kyota, Japan) in outpatients with ≥ 1 cardiovascular risk. PAD was defined as ABI ≤ 0.9. Among 2309 outpatients (mean age 62.4 years), worse renal function was associated with higher brachial-ankle PWV, heart-carotid PWV, heart-femoral PWV (hf-PWV), and lower ABI (all P < .001). Multivariate regression models showed independent associations between lower eGFR, lower ABI (Coef: 0.42 & 0.41 for right and left), higher hf-PWV (Coef: -11.4 [95% CI: -15.4, -7.3]) and greater PAD risk (adjusted OR: 0.83 [95% CI: 0.76, 0.91], all P < .05). eGFR set at 77 mL/min/1.73m2 was observed to be useful clinical cutoff (c-statistics: 0.67) for identifying PAD (P for ΔAUROC: .009; likelihood X2 : 93.82 to 137.43, P < .001) when superimposed on clinical risks. This study suggested early renal insufficiency is tightly linked to region-specific vascular stiffness and PAD.

7.
Int J Cardiol ; 231: 195-200, 2017 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-28087179

RESUMO

BACKGROUND: The relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac structural or functional anomalies in pre-clinical, asymptomatic Asian populations has not been well identified. METHODS: From October 2005 to March 2008, we enrolled consecutive asymptomatic adults with preserved global left ventricular (LV) function (ejection fraction>50%) who underwent annual cardiovascular health survey. Circulating NT-proBNP was used to identify echo-defined cardiac structural/functional anomalies and compared to current recommended cut-off from the European Society of Heart Failure. RESULTS: Among 976 eligible subjects, 371 (38%) had structural heart diseases. Echocardiography-based left atrial diameter (Coef: 71.2), diastolic dysfunction (Coef: 35.4), and presence of pulmonary hypertension (Coef: 83.1) or valvular heart disease (Coef: 56.1, all p<0.05) of any form independently predicted circulating NT-ProBNP. NT-ProBNP cut-off values of 32.8 and 115.4pg/ml for subjects aged ≤ and >75years, respectively, demonstrated areas under the receiver operating characteristic curve of 0.76 (95% CI: 0.73-0.80) and 0.70 (95% CI: 0.52-0.88) for predicting structural or functional anomaly. CONCLUSION: We examined the feasibility of NT-ProBNP for identifying cardiac structural and functional anomaly in an asymptomatic ethnic Taiwanese population with a relatively lower cut-off value, indicating its potential role for pre-clinical screening of Asian patients.


Assuntos
Inquéritos Epidemiológicos , Cardiopatias/sangue , Ventrículos do Coração/fisiopatologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Guias de Prática Clínica como Assunto , Doenças Assintomáticas , Biomarcadores/sangue , Cardiologia , Ecocardiografia Doppler , Europa (Continente) , Feminino , Seguimentos , Cardiopatias/epidemiologia , Cardiopatias/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Curva ROC , Estudos Retrospectivos , Sociedades Médicas , Sístole , Taiwan/epidemiologia , Função Ventricular Esquerda
8.
BMC Cardiovasc Disord ; 15: 142, 2015 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-26518903

RESUMO

BACKGROUND: Visceral adipose tissue, a biologically active fat depot, has been proposed as a reliable marker for visceral adiposity and metabolic abnormalities. Effects of such adiposity on LV diastolic function and dyssynchrony remained largely unknown. METHODS: We assessed pericardial fat (PCF) and thoracic peri-aortic fat (TPAF) by three-dimensional (3D) volume-vender multi-detector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Echo-derived diastolic parameters and tissue Doppler imaging (TDI) defined mitral annular systolic (S'), early diastolic (E') velocities as well as LV filling (E/E') were all obtained. Intra-ventricular systolic (Sys-D) and diastolic (Dias-D) dyssynchrony were assessed by TDI method. RESULTS: A total of 318 asymptomatic subjects (mean age: 53.5 years, 36.8 % female) were eligible in this study. Greater PCF and TPAF were both associated with unfavorable diastolic indices and higher diastolic dyssynchrony (all p < 0.05). These associations remained relatively unchanged in multi-variate models. PCF and TPAF set at 81.68 & 8.11 ml yielded the largest sensitivity and specificity (78.6 and 60 % for PCF, 75 and 66.6 % for TPAF, respectively) in predicting abnormally high LV diastolic dyssynchrony, which was defined as Dias-D≧55 ms. CONCLUSION: Increasing visceral adiposity may be associated with adverse effects on myocardium, primarily featured by worse diastolic function and greater degree of dyssynchrony.


Assuntos
Tomografia Computadorizada Multidetectores , Obesidade Abdominal/diagnóstico por imagem , Obesidade Abdominal/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adiposidade/fisiologia , Doenças Assintomáticas , Diástole/fisiologia , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/diagnóstico por imagem
9.
PLoS One ; 9(12): e115260, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25545637

RESUMO

BACKGROUND: Three dimensional (3D) echocardiography-derived measurements of myocardial deformation and twist have recently advanced as novel clinical tools. However, with the exception of left ventricular ejection fraction and mass quantifications in hypertension and heart failure populations, the prognostic value of such imaging techniques remains largely unexplored. METHODS: We studied 200 subjects (mean age: 60.2±16 years, 54% female, female n = 107) with known hypertension (n = 51), diastolic heart failure (n = 61), or systolic heart failure (n = 30), recruited from heart failure outpatient clinics. Fifty-eight healthy volunteers were used as a control group. All participants underwent 3D-based myocardial deformation and twist analysis (Artida, Toshiba Medical Systems, Tokyo, Japan). We further investigated associations between these measures and brain natriuretic peptide levels and clinical outcomes. RESULTS: The global 3D strain measurements of the healthy, hypertension, diastolic heart failure, and systolic heart failure groups were 28.03%, 24.43%, 19.70%, and 11.95%, respectively (all p<0.001). Global twist measurements were estimated to be 9.49°, 9.77°, 8.32°, and 4.56°, respectively. We observed significant differences regarding 3D-derived longitudinal, radial, and global 3D strains between the different disease categories (p<0.05), even when age, gender, BMI and heart rate were matched. In addition, 3D-derived longitudinal, circumferential, and 3D strains were all highly correlated with brain natriuretic peptide levels (p<0.001). At a mean 567.7 days follow-up (25th-75th IQR: 197-909 days), poorer 3D-derived longitudinal, radial, and global 3D strain measurements remained independently associated with a higher risk of cardiovascular related death or hospitalization due to heart failure, after adjusting for age, gender, and left ventricular ejection fraction (all p<0.05). CONCLUSIONS: 3D-based strain analysis may be a feasible and useful diagnostic tool for discriminating the extent of myocardial dysfunction. Furthermore, it is able to provide a prognostic value beyond traditional echocardiographic parameters in terms of ejection fraction.


Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Peptídeo Natriurético Encefálico/sangue , Função Ventricular , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Ecocardiografia Doppler , Ecocardiografia Tridimensional , Feminino , Insuficiência Cardíaca/sangue , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade
10.
Clin Cardiol ; 37(3): 172-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24399410

RESUMO

BACKGROUND: The effect of body fat distribution on left ventricular (LV) mass and geometry has been recently recognized. However, data regarding circulating inflammatory markers in relation to regional visceral fat deposits, which are metabolically active tissues that can impact cardiac structural remodeling, remain sparse. HYPOTHESIS: We hypothesized that obesity has adverse effects on cardiac function and structure. METHODS: We consecutively studied 1071 asymptomatic subjects (age 49.5 ± 10.5 years, 39.4% female) free from significant valvular disorders, chronic lung disease, or renal disease. Echocardiography-defined cardiac structures and LV geometries including LV mass, mass-to-volume ratio, and fractional shortening were all determined. Body fat composition (Tanita-305 Body-Fat Analyzer; Tanita Corp., Tokyo, Japan) was obtained and calculated. Multivariate regression models from various models were used to represent the independent association between body fat and echo-derived ventricular mass and geometries. RESULTS: In multivariable analysis, increasing body fat was significantly related to increase in left atrial (LA) and LV diameter, posterior wall thickness, relative wall thickness (RWT), LV mass, mass-to-volume ratio, and decreased midwall fractional shortening with or without stress correction (all P < 0.001). When LV mass and severity of mitral regurgitation was further added, the independent association between increased body fat composition and larger LA diameter remained significant (ß coefficient = 0.37, P < 0.001). Elevated high-sensitivity C-reactive protein (Hs-CRP) level was associated with larger LA diameter, increased RWT, and worsened midwall mechanics in the female gender (all interaction P < 0.05). CONCLUSIONS: Accumulated body fat seemed to be related to worse ventricular midwall contractility and atrial remodeling, particularly in the female gender, with high systemic inflammation. These gender and Hs-CRP-specific modification effects may potentiate the pathological mechanisms involved in heart failure with preserved ejection fraction.


Assuntos
Remodelamento Atrial/fisiologia , Distribuição da Gordura Corporal , Proteína C-Reativa/análise , Valvas Cardíacas/diagnóstico por imagem , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contração Miocárdica/fisiologia , Estudos Retrospectivos , Fatores Sexuais , Ultrassonografia
11.
Biomark Res ; 1(1): 25, 2013 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-24252645

RESUMO

Carbohydrate antigen 125 (CA-125), traditionally a tumor marker for screening, diagnosis, and monitoring in ovarian malignancy, had recently been shown increasing evidence and more extensively recognized/explored as a novel surrogate of heart failure (HF). The exact mechanisms underlying the pathophysiologic link between elevated serum CA-125 concentration and HF may be multi-factorial, with both mechanical and inflammatory process including numerous potential cytokines involved. Accumulating data had consistently indicated its diagnostic and prognostic role in HF patients in various clinical settings, however, there is limited clinical information regarding the incremental value or head-to-head comparison of such marker to other well-established HF markers. In this brief review, we aimed to discuss the biosynthesis, and potential insights of underlying pathophysiologies associated with CA-125 secretion in the scenarios of cardiac structural/functional alterations and HF, and further explored its current usage and roles in several recent reports.

12.
Am J Cardiol ; 110(7): 993-1000, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22728006

RESUMO

Carbohydrate antigen-125 (CA-125) has recently been reported to correlate with the severity of systolic heart failure (HF). However, the association between this marker and HF with preserved ejection fraction (HFpEF) remains elusive. We studied 158 consecutive women with preserved ejection fraction, who were categorized into 3 groups: those with HF (HFpEF group, n = 35), those with ≥1 cardiovascular risk (at-risk group, n = 78), and 45 normal controls (n = 45). All subjects underwent echocardiography with serum N-terminal pro-brain type natriuretic peptide (NT-ProBNP), CA-125 level, and other tumor markers obtained. HFpEF group showed significantly greater baseline levels of CA-125 and NT-ProBNP than both normal and at-risk groups (p <0.05). In addition, the serum CA-125 level correlated with the maximum left atrial volume (r = 0.24, p = 0.002). During a mean follow-up of 828.1 days (interquartile range 38 to 1,504.5), those with CA-125 levels >17.29 U/ml had a greatest incidence of HF hospitalization (hazard ratio 6.2, p <0.01) and remained an independent prognosticator in the multivariate Cox models. CA-125 superimposed on NT-ProBNP successfully expanded the receiver operating characteristic curve further in predicting HF hospitalization (area under curve 0.72 to 0.82, c-statistic 0.0049). In conclusion, serum CA-125 might serve as a novel biomarker for HFpEF and predicting HF hospitalization in women.


Assuntos
Função do Átrio Esquerdo/fisiologia , Antígeno Ca-125/sangue , Insuficiência Cardíaca/fisiopatologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda , Adulto , Idoso , Biomarcadores/sangue , Ecocardiografia , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Humanos , Imunoensaio , Pessoa de Meia-Idade , Prognóstico , Pressão Propulsora Pulmonar , Estudos Retrospectivos , Adulto Jovem
13.
Echocardiography ; 28(6): 665-75, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21718355

RESUMO

BACKGROUND: Determinants of functional mitral regurgitation (FMR) severity after acute anterior myocardial infarction (MI) remained unclear. Our aim was to: (1) test whether LV dyssynchrony upon real time three-dimensional echocardiography (RT-3DE) is independently associated with FMR severity; and (2) to investigate the role of regional systolic dyssynchrony index (SDI) in identifying FMR severity. METHODS: RT-3DE was successfully performed on 64 consecutive patients following acute anterior MI with a narrow QRS complex (<130 ms) and another 30 healthy volunteers. MR severity was assessed using vena contracta method. SDI was derived from the dispersion of the time to minimum regional volume for all 16 LV segments. Multiple linear regression analysis was used to identify the independent relationship between FMR and SDI with and without multivariate adjustment. RESULTS: The mean LV ejection fraction was 49.6%± 11.9% in the MI group. All regional (except apical) and global SDIs were associated with regional LV remodeling and were significantly correlated with FMR even after multivariate adjustment, with midwall SDI being most strongly associated with MR severity (R(2) = 0.55, P < 0.001). Regional midwall SDI superimposed on LV global geometry and mitral leaflet deformation substantially expanded the area under curve in identifying FMR (AUC increased from 0.69 to 0.93, c-statistics: P = 0.041). CONCLUSIONS: While both global and regional dyssynchrony following anterior MI were independently related to FMR severity, regional midwall dyssynchrony further added incremental value in predicting FMR severity beyond traditional parameters. This finding provides a new insight into the understanding of FMR after anterior MI and may further potentiate specific therapeutic approaches.


Assuntos
Ecocardiografia Tridimensional/métodos , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Idoso , Sistemas de Computação , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
BMC Cell Biol ; 12: 19, 2011 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-21575204

RESUMO

BACKGROUND: Advanced glycation end products generated in the circulation of diabetic patients were reported to affect the function of vascular wall. We examined the effects of advanced glycation end products-bovine serum albumin (AGE-BSA) on endothelial connexin43 (Cx43) expression and gap-junction communication. RESULTS: In human aortic endothelial cells (HAEC) treated with a series concentrations of AGE-BSA (0-500 µg/ml) for 24 and 48 hours, Cx43 transcript and Cx43 protein were reduced in a dose dependent manner. In addition, gap-junction communication was reduced. To clarify the mechanisms underlying the down-regulation, MAPKs pathways in HAEC were examined. Both a MEK1 inhibitor (PD98059) and a p38 MAPK inhibitor (SB203580) significantly reversed the reductions of Cx43 mRNA and protein induced by AGE-BSA. Consistently, phosphorylation of ERK and p38 MAPK was enhanced in response to exposure to AGE-BSA. However, all reversions of down-regulated Cx43 by inhibitors did not restore the functional gap-junction communication. CONCLUSIONS: AGE-BSA down-regulated Cx43 expression in HAEC, mainly through reduced Cx43 transcription, and the process involved activation of ERK and p38 MAPK.


Assuntos
Conexina 43/metabolismo , Células Endoteliais/metabolismo , Junções Comunicantes/fisiologia , Produtos Finais de Glicação Avançada/química , Soroalbumina Bovina/química , Animais , Bovinos , Células Cultivadas , Conexina 43/genética , Regulação para Baixo , Flavonoides/farmacologia , Junções Comunicantes/metabolismo , Produtos Finais de Glicação Avançada/farmacologia , Humanos , Imidazóis/farmacologia , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 1/metabolismo , Fosforilação , Piridinas/farmacologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Circ Cardiovasc Imaging ; 1(1): 6-13, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19808509

RESUMO

BACKGROUND: We tested the hypothesis that multimodality imaging of mouse embryonic stem cells (mESCs) provides accurate assessment of cellular location, viability, and restorative potential after transplantation into different zones of myocardial infarction. METHODS AND RESULTS: Mice underwent left anterior descending artery ligation followed by transplantation of dual-labeled mESCs with superparamagnetic iron oxide and luciferase via direct injection into 3 different zones of myocardial infarction: intra-infarction, peri-infarction, and normal (remote). One day after transplantation, magnetic resonance imaging enabled assessment of the precise anatomic locations of mESCs. Bioluminescence imaging allowed longitudinal analysis of cell viability through detection of luciferase activity. Subsequent evaluation of myocardial regeneration and functional restoration was performed by echocardiography and pressure-volume loop analysis. Using 16-segment analysis, we demonstrated precise localization of dual-labeled mESCs. A strong correlation between histology and magnetic resonance imaging was established (r=0.962, P=0.002). Bioluminescent imaging data demonstrated that cell viability in the remote group was significantly higher than in other groups. Echocardiography and pressure-volume loop analysis revealed improved functional restoration in animals treated with mESCs, although myocardial regeneration was not observed. CONCLUSIONS: Multimodality evaluation of mESC engraftment in the heterogeneous tissue of myocardial infarction is possible. Magnetic resonance imaging demonstrated accurate anatomic localization of dual-labeled mESCs. Bioluminescent imaging enabled assessment of variable viability of mESCs transplanted into the infarcted myocardium. Echocardiography and pressure-volume loop analysis validated the restorative potential of mESCs. Although mESCs transplanted into the remote zone demonstrated the highest viability, precise delivery of mESCs into the peri-infarction region might be equally critical in restoring the injured myocardium.


Assuntos
Células-Tronco Embrionárias/transplante , Infarto do Miocárdio/cirurgia , Miocárdio/patologia , Transplante de Células-Tronco , Animais , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Meios de Contraste , Dextranos , Modelos Animais de Doenças , Ecocardiografia , Estudos de Viabilidade , Feminino , Óxido Ferroso-Férrico , Luciferases/genética , Imagem por Ressonância Magnética , Nanopartículas de Magnetita , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Recuperação de Função Fisiológica , Regeneração , Fatores de Tempo , Transfecção , Função Ventricular Esquerda , Pressão Ventricular
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