RESUMO
PURPOSE: To investigate the toxic effect of oscillating high glucose (OHG) versus persistent high glucose (PHG) in inducing oxidative stress and cellular apoptosis in human coronary artery endothelial cells (HCAECs) in vitro. METHODS: HCAECs were incubated for 72 h continuously in normal glucose (5.5 mmol/L glucose), PHG (25 mmol/L glucose), OHG (5.5 mmol and 25 glucose mmol/L alternating every 6 h) and mannitol, respectively. Cellular viability, concentration of oxidative stress biomarkers (MDA and GSH) in the supernatants of cell culture, and intracellular ROS level were quantitated after exposure to different concentrations of glucose for a total 72 h. Apoptosis of HCAECs cultured with various glucose levels was evaluated by annexin V-FITC and PI staining followed by analysis with flow cytometry. The expressions of HO-1 and Nrf2 were measured by RT-qPCR and Western blotting at the end of the experiment. RESULTS: HCAECs cultured with PHG showed decreased cellular viability compared to those with normal level of glucose (p < 0.05). The decrease was more pronounced under OHG condition (p < 0.05). Cellular oxidative stress was provoked in HCAECs exposed to PHG with marked increased MDA level, reduced GSH concentration and elevated ROS production (p < 0.05). The stress was further amplified in the setting of OHG (p < 0.05). The cellular apoptosis was enhanced by culturing with PHG, and to a greater extent when incubated with OHG. Both expressions of HO-1 and Nrf2 were suppressed in HCAECs in persistent hyperglycemia condition, while the inhibition was more intense in the fluctuating hyperglycemia condition (p < 0.05). CONCLUSIONS: These findings indicate that OHG could be more detrimental to HCAECs than PHG. This is probably due to the enhancement of oxidative stress and cellular apoptosis induced by frequent glucose swings through the inhibition of Nrf2/HO-1 pathway.
Assuntos
Apoptose/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Glucose/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Vasos Coronários/citologia , Vasos Coronários/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Glutationa/metabolismo , Humanos , Malondialdeído/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
PURPOSE: This study was to investigate whether high pericardial adipose tissue (PAT) volume is related to the presence and severity of coronary artery disease (CAD). METHODS: Consecutive patients (310 patients) who underwent both dual-source 64-slice CT and percutaneous coronary angiography were recruited into this study. Waist circumference (WC), body mass index (BMI), blood biochemical variables, coronary artery calcium (CAC) score and Gensini score were measured. Pericardial adipose tissue (PAT) volume was determined by dual-source CT. RESULTS: PAT volume was positively correlated with BMI, WC, gender (male), hypertension, diabetes, age, total cholesterol and low-density lipoprotein-cholesterol. PAT volume in CAD patients was significantly higher than that in patients without CAD (238.36 ± 81.21 cm3 vs. 200.13±72.34 cm3). PAT volumes in patients with multi-vessel lesions were significantly higher than those with one-vessel lesions (P < 0.001). A significant correlation between PAT volume and CAC score (r=0.305, P < 0.001) was found. PAT volume was an independent factor affecting Gensini score. CONCLUSION: PAT volume was significantly correlated with traditional cardiovascular risk factors, the severity of coronary atherosclerosis and the number of stenotic coronary vessels. Thus, PAT volume may be a reliable marker to evaluate the presence and severity of CAD.
Assuntos
Tecido Adiposo/patologia , Doença da Artéria Coronariana/patologia , Pericárdio/patologia , Tecido Adiposo/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pericárdio/diagnóstico por imagem , RadiografiaRESUMO
OBJECTIVE: To compare coronary lesion characteristics by coronary angiography (CAG) between yellows and whites. METHODS: CAG results of 3021 Chinese patients, defined as yellows, from Nanjing and 3230 Australian patients, defined as whites, from Sydney were analyzed. The coronary artery lesion was evaluated by the number and location of coronary lesion and Gensini scores. RESULTS: (1) Coronary stenosis was diagnosed in 69.4% Chinese patients and 75.5% in Australians. The involved coronary arteries were left anterior descending branch, right coronary artery, left circumflex branch and left main coronary artery in a descending order in both Chinese and Australians. (2) The incidences of three-vessel disease and left main disease of yellows were significantly lower than that of whites in both male (29.8% vs. 34.0% and 9.6% vs. 14.2%) and female patients (15.8% vs. 26.2% and 4.9% vs. 11.6%) respectively, all P < 0.05. (3) There was an age-dependent Gensini scores increase in both yellows and whites patients and Gensini scores at age 40 and more of whites were significantly higher than those of yellows in comparable age groups. CONCLUSION: The incidences of three-vessel disease and left main disease as well as Gensini score were significantly higher in Australian patients than those of Chinese patients.
Assuntos
Doença da Artéria Coronariana/etnologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Austrália/epidemiologia , China/epidemiologia , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , População Branca , Adulto JovemRESUMO
OBJECTIVE: To investigate the correlation of CTRP9 with coronary atherosclerosis. METHODS: Coronary angiography confirmed CAD in 241 patients (62 received CABG) and non-CAD in 121 (55 received valve replacement). RESULTS: Serum levels of LDL-C, CRP, TNF-α, IL-6, and leptin in CAD patients were significantly higher than those in non-CAD patients (P < 0.05), but APN and CTRP9 were lower (P < 0.05). Serum levels of CTRP9 and APN were negatively related to BMI, HOMA-IR, TNF-α, IL-6, and leptin but positively to HDL-C (P < 0.05) in CAD patients. After adjustment of APN, CTRP9 was still related to the above parameters. Serum CTRP9 was a protective factor of CAD (P < 0.05). When compared with non-CAD patients, leptin mRNA expression increased dramatically, while CTRP9 mRNA expression reduced markedly in epicardial adipose tissue of CAD patients (P < 0.05). The leptin expression and macrophage count in CAD group were significantly higher than in non-CAD group, but CAD patients had a markedly lower CTRP9 expression (P < 0.05). CONCLUSIONS: Circulating and coronary CTRP9 plays an important role in the inflammation and coronary atherosclerosis of CAD patients. Serum CTRP9 is an independent protective factor of CAD.
Assuntos
Adiponectina/genética , Doença da Artéria Coronariana/genética , Glicoproteínas/genética , Leptina/genética , Adiponectina/biossíntese , Adiponectina/sangue , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Idoso , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Feminino , Regulação da Expressão Gênica , Estudos de Associação Genética , Glicoproteínas/biossíntese , Glicoproteínas/sangue , Humanos , Leptina/biossíntese , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Pericárdio/metabolismo , Pericárdio/patologia , RNA Mensageiro/biossíntese , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose TumoralRESUMO
OBJECTIVE: To investigate the phenotype conversion of epicardial adipocytes and its potential molecular mechanism during the occurrence and development of coronary atherosclerosis. METHODS: A total of 30 health male New Zealand white rabbits were used. In experiment group (n=15), rabbits were fed with high fat food to establish atherosclerosis animal model; rabbits in control group (n=15) were fed with normal food. RESULTS: At week 0, UCP-1 and PPARγ mRNA expressions in EAT and sBAT were significantly higher than in eWAT, and leptin mRNA expression lower than (P<0.05). In experiment group, the mRNA expressions of UCP-1 and PPARγ reduced gradually, but leptin mRNA increased progressively in EAT (P<0.05). UCP-1 expression reduced gradually, the newly generated blood vessels reduced significantly, but leptin and RAM11 increased gradually (P<0.05). The adipocyte volume in EAT increased gradually, but the adipocyte number reduced progressively (P<0.05). The number of mitochondria with multiple crests reduced gradually in EAT; IL-6 reduced the mRNA expressions of UCP-1 and PPARγ in adipocytes of BAT in a dose dependent manner, but it increased the mRNA expressions of leptin and STAT3 (P<0.05). In the presence of IL-6, JSI-124 increased the mRNA expressions of UCP-1 and PPAR-γ in adipocytes of BAT in a dose dependent manner, but it reduced the mRNA expressions of leptin and STAT3 (P<0.05). CONCLUSION: During the progression of atherosclerosis, there is a phenotype conversion of EAT from BAT to WAT, which further promotes the focal occurrence and development of atherosclerosis; IL-6 may activate JAK-STAT3 pathway to induce this conversion.