RESUMO
OBJECTIVE: Gastrodin, a glucoside of gastrodigenin, inhibits cerebral oxidant stress and apoptosis in multiple central nervous system injury, but its effect in intracerebral hemorrhage (ICH) remains unclear. This study investigated the effect of gastrodin on neuronal apoptosis and neurological deficits in rat ICH model. METHODS: In vitro experiments were performed using hematoma lysate-induced cell damage model in primary cortical neurons. Rat ICH model was produced by a caudatum injection of collagenase. Gastrodin was intraperitoneal injected after 2 hours following ICH. Cell viability, brain water content, neurological score, western blot, and immunofluorescence experiments were performed. RESULTS: Gastrodin significantly decreased hematoma lysate-induced reduction of cell viability and cell apoptosis in primary cortical neurons. Gastrodin significantly improved brain edema and neurological deficits post-ICH. Moreover, gastrodin administration significantly reduced levels of ROS, 8-OHDG, 3-Nitrotyrosine and MDA, while increased GSH-Px and SOD activity, and stimulated the upregulation of Keap1, Nrf2, and HO-1 signaling at 72 hours post-ICH. Furthermore, gastrodin significantly increased Bcl-2 expression, while reduced level of Bax, active caspase-3 and active caspase-9, also reduced the number of active caspase-3 or TUNEL positive neurons at 72 hours post-ICH. CONCLUSION: These results suggest that gastrodin is neuroprotective after ICH and the mechanism may be associated with the inhibition of oxidative stress and neuronal apoptosis.
Assuntos
Apoptose/efeitos dos fármacos , Álcoois Benzílicos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Hemorragia Cerebral/tratamento farmacológico , Glucosídeos/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Comportamento Animal/efeitos dos fármacos , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Edema Encefálico/prevenção & controle , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Modelos Animais de Doenças , Masculino , Atividade Motora/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
BACKGROUND: MMP 14 is expressed in atherosclerotic plaques and potentially plays an important role in the development of vulnerable carotid plaques. MMP 14 gene polymorphisms can influence the bioactivity or expression of MMP 14. OBJECTIVE: The aim of this study was to investigate the association between MMP 14 position + 7096 T > C (NM_004995.2:c.855T> C, rs2236307) polymorphism and vulnerable carotid plaque formation. METHODS: 1370 patients with ischemic cerebral infarctions were enrolled and divided into three groups according to their carotid ultrasound examination: No plaque group (n = 346), stable plaque group (n = 695) and vulnerable plaque group (n = 329). The traditional atherosclerosis risk factors were recorded, and the MMP 14 polymorphism were genotyped by Applied Biosystems 7300 Real-Time PCR System using the TaqMan assay. RESULTS: In the multiple logistic regression analysis done among the sub-groups, compared to no carotid plaque group, individuals with the MMP 14 position + 7096 TC+ CC genotype showed a significantly (p = 0.009) lower risk for vulnerable plaque (AOR = 0.675; 95% CI, 0.568-0.922) formation compared with subjects of the TT genotype; however, no relation between TC+ CC genotype and stable carotid plaque was observed (p > 0.125). Age was a risk factor for both stable plaque (p = 0.000; AOR = 3.732; 95% CI: 2.496-5.58) and vulnerable plaque formation (p = 0.001; AOR = 2.234; 95% CI: 1.387-3.597). Meanwhile, fibrinogen (> 4.0 g/L) was a risk factor for stable plaque (p = 0.004; AOR = 2.313; 95% CI: 1.308-4.091). CONCLUSIONS: The MMP 14 position + 7096 TC+ CC genotype might lower the risk of vulnerable carotid plaque formation. Fibrinogen (> 4.0 g/L) was a risk factor for stable plaque.
Assuntos
Aterosclerose/genética , Infarto Cerebral/genética , Metaloproteinase 14 da Matriz/genética , Placa Aterosclerótica/genética , Polimorfismo Genético , Fatores Etários , Idoso , Povo Asiático , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/etnologia , Biomarcadores/sangue , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Infarto Cerebral/sangue , Infarto Cerebral/diagnóstico , Infarto Cerebral/etnologia , Feminino , Fibrinogênio/metabolismo , Expressão Gênica , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/diagnóstico , Placa Aterosclerótica/etnologia , Fatores de RiscoRESUMO
OBJECTIVE: To assess the association between 2 single nucleotide polymorphisms (SNPs) located in exonic regions of matrix metalloproteinase-10 (MMP-10) gene and instability of carotid plaques in a Han Chinese population. METHODS: Five hundred and eighty-five patients were divided into carotid vulnerable plaque group (n=206) and stable plaque group (n=379) based on results of carotid B-mode ultrasonography. The SNPs were genotyped by real-time polymerase chain reaction using an ABI 7300 TaqMan platform. RESULTS: The distribution of rs17435959 between the two groups was significantly different at both genotypic (GC+CC vs. GG, P=0.006, OR=2.012) and allelic levels (C vs. G, P=0.001,OR=2.160). Above differences have remained significant with binary logistic regression analysis (P=0.007, OR=2.022; P=0.002, OR=2.104). The minor allele frequency of rs17293607 was 0.56%. CONCLUSION: Above findings suggested that rs17435959 of the MMP-10 gene is associated with carotid vulnerable plaque in ethnic Chinese Hans. The C allele may be a susceptible predictor for carotid vulnerable plaque.
Assuntos
Metaloproteinase 10 da Matriz/genética , Placa Aterosclerótica/genética , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/enzimologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: To investigate the association between a -799C/T polymorphism in the promotor region of matrix metalloproteinase-8 (MMP-8) gene and instability of carotid plaque in Chinese Han population. METHODS: A total of 451 acute infarction patients from the Department of Neurology of Taizhou Hospital were divided into carotid vulnerable plaque group and carotid stable plaque group according to the results of carotid B-mode ultrasonography. Serum MMP -8 level was measured by the means of enzyme-linked immunosorbent assay (ELISA). At the same time, the MMP-8 -799C/T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Serum level of MMP-8 in the carotid vulnerable plaque group was higher than that in the carotid stable plaque group (t= 2.894, P= 0.004). The genotype distribution of -799C/T polymorphism between the two groups was significantly different (Chi-square = 13.65, P= 0.000). Serum level of MMP-8 in patients with TT genotype was higher than that in patients with CC genotype (t= 3.141, P= 0.001). CONCLUSION: The present study suggested that serum level of MMP-8 and the -799C/T polymorphism of MMP-8 gene are associated with carotid vulnerable plaque in Chinese Han population, and the T allele may be a predictor for the susceptibility of carotid vulnerable plaque.
Assuntos
Metaloproteinase 8 da Matriz/genética , Placa Aterosclerótica/genética , Idoso , Sequência de Bases , Feminino , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Placa Aterosclerótica/enzimologia , Placa Aterosclerótica/patologia , Polimorfismo Genético , Regiões Promotoras GenéticasRESUMO
OBJECTIVE: To identify spatial distribution and risk factors among tuberculosis (TB) cases in Songjiang district, Shanghai, 2006 - 2009. METHODS: All active TB cases and all bacteriologically confirmed TB cases diagnosed during the period from 2006 to 2009 were recruited into the study. Spatial scan statistics were used to identify spatial clusters. Using logistic regression, we compared the demographic and clinical characteristics of TB cases in spatial clusters versus TB cases not in spatial clusters. RESULTS: A total of 1815 active TB cases and 730 bacteriologically confirmed TB cases were recruited during 2006 - 2009. Chedun township and Xinqiao township was detected to be a spatial cluste (RR = 1.38, LLR = 16.78, P < 0.01), which was the location of the municipal industrial zone. No spatial cluster was found during 2006 - 2007, while during 2008 - 2009 Chedun township was detected to be a spatial cluster (RR = 1.70, LLR = 15.06, P < 0.01). Among resident population, the spatial cluster of TB cases was located in the southwestern part of Songjiang district, which included five townships Xinbang, Shihudang, Xiaokunshan, Maogang and Yongfeng (RR = 1.49, LLR = 10.52, P < 0.01); while among migrant population, the spatial cluster of TB cases was located in Chedun township (RR = 1.55, LLR = 15.64, P < 0.01). There were higher proportions of resident TB cases who were farmers (AOR = 4.9, 95%CI: 1.9 - 12.3) or had other occupations (AOR = 2.6, 95%CI: 1.1 - 5.9) in the spatial cluster. There were higher proportions of migrant TB cases who lived here for less than 5 years (< 1 year: AOR = 5.9, 95%CI: 1.8 - 19.5; 1 - 5 years: AOR = 3.2, 95%CI: 1.0 - 9.9) or worked at other occupations (AOR = 2.8, 95%CI: 1.5 - 5.1) and lower proportions of migrant TB cases who came from Eastern region (AOR = 0.3, 95%CI: 0.1 - 0.8) or Middle region (AOR = 0.5, 95%CI: 0.3 - 0.9) in the spatial cluster. CONCLUSION: In Songjiang district there was a spatial cluster in TB cases, which was Chedun township. Local residents with TB who were farmers or had other occupations were more likely to be in the spatial cluster. Migrants with TB who lived here for less than 5 years or came from Western region were more likely to be in the spatial cluster.
Assuntos
Tuberculose/epidemiologia , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Conglomerados Espaço-Temporais , Migrantes , Tuberculose Pulmonar/epidemiologiaRESUMO
Carbohydrates represent one of the most significant natural building blocks, which govern numerous critical biological and pathological processes through specific carbohydrate-receptor interactions on the cell surface. We present here a new class of electrochemical probes based on gold surface-coated epimeric monosaccharide-quinone hybrids toward the ingenious detection of specific epimeric carbohydrate-protein interactions. Glucose and galactose, which represent a pair of natural monosaccharide C4 epimers, were used to closely and solidly conjugate with the 1,4-dimethoxybenzene moiety via a single C-C glycosidic bond, followed by the introduction of a sulfhydryl anchor. The functionalized aryl C-glycosides were sequentially coated on the gold electrode via the self-assembled monolayer (SAM) technique. X-ray photoelectron spectroscopy (XPS) was used to confirm the SAM formation, by which different binding energies (BE) between the glucosyl and the galactosyl SAMs on the surface, probably rendered by their epimeric identity, were observed. The subsequent electrochemical deprotection process readily furnished the surface-confined quinone/hydroquinone redox couple, leading to the formation of electrochemically active epimeric monosaccharide-quinone SAMs on the gold electrode. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) used for the detection of specific sugar-lectin interactions indicated that the addition of specific lectin to the corresponding monosaccharide-quinone surface, i.e., concanavalin A (Con A) to the glucosyl SAM and peanut agglutinin (PNA) to the galactosyl SAM, resulted in an obvious decrease in peak current, whereas the addition of nonspecific lectins to the same SAMs gave very minor current variations. Such data suggested our uniquely constructed gold surface coated by sugar-quinone hybrids to be applicable as electrochemical probes for the detection of specific sugar-protein interactions, presumably leading to a new electrochemistry platform toward the study of carbohydrate-mediated intercellular recognitions.
Assuntos
Benzoquinonas/química , Galactose/química , Glucose/química , Ouro/química , Lectinas/química , Carboidratos/química , Técnicas Eletroquímicas , Eletrodos , Espectroscopia FotoeletrônicaRESUMO
The aim of the current study was to explore the possible association of the polymorphism of C(-735)T in MMP-2 with the vulnerable plaque risk in ultrasound-confirmed carotid atherosclerosis cases. Serum MMP-2 levels were measured to investigate the relationship between the MMP-2 level and the genetic variability. The MMP-2 polymorphism was detected by PCR-RFLP in the 243 cases with stable plaque and 221 cases with vulnerable plaque. Serum MMP-2 levels were measured with ELISA. The results showed that MMP-2 was significantly higher in the cases with vulnerable plaque than in the cases with stable plaque. A statistical difference was found between the genotype distributions in the vulnerable plaque cases and that in the stable cases. T-allele frequency was also found to be over-represented in the stable plaque cases than in the vulnerable plaque cases, which might partially explain the observed difference in the serum MMP-2 levels in the different plaque cases. The current results also suggested that MMP-2 was a risk factor in the cases with vulnerable plaques, whereas TT genotype and T allele might be protective factors in the cases with vulnerable plaques.
Assuntos
Povo Asiático/genética , Doenças das Artérias Carótidas/genética , Predisposição Genética para Doença , Metaloproteinase 2 da Matriz/genética , Placa Aterosclerótica/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Doenças das Artérias Carótidas/etnologia , Doenças das Artérias Carótidas/fisiopatologia , China , Feminino , Genótipo , Hemodinâmica , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Placa Aterosclerótica/etnologia , Placa Aterosclerótica/fisiopatologia , Polimorfismo de Fragmento de RestriçãoRESUMO
BACKGROUND: Matrix metalloproteinase-7 (MMP-7) may play an important role in the development of vulnerable carotid plaque. An A-to-G transition (-181A/G) in the promoter region of MMP7 is functional in vitro by altering the transcriptional activity of the gene. The aim of this study was to investigate the association between the MMP7 -181A/G polymorphism and vulnerable carotid plaque formation. METHODS: The authors enrolled 641 patients and divided them into three groups according to the carotid ultrasound examination: vulnerable plaque group (n=118), stable plaque group (n=385) and no plaque group (n=138). Traditional atherosclerosis risk factors were recorded and the MMP7 -181A/G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In the multinomial logistic regression analysis, compared to the no plaque group, no relationship between MMP7 -181AG+GG genotypes and stable carotid plaque was observed [odds ratio (OR) 1.50; p=0.239]. However, the frequency of AG+GG genotypes was significantly higher in the vulnerable plaque group (OR 2.74; p=0.008). Age was a risk factor for plaque formation, while statin treatment can reduce the prevalence of atherosclerotic plaque. Additionally, using binary logistic regression analysis between the stable and vulnerable plaque groups, this MMP7 polymorphism was associated with vulnerable plaque independently of other factors [OR 1.83; 95% confidence interval 1.08- 3.11; p=0.026]. CONCLUSIONS: The MMP7 -181A/G polymorphism is associated with the development of vulnerable carotid plaques. Age is a risk factor for plaque formation, while statin therapy is associated with a decreased prevalence of carotid atheromatous plaques.
Assuntos
Povo Asiático/genética , Predisposição Genética para Doença , Metaloproteinase 7 da Matriz/genética , Placa Aterosclerótica/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de ReferênciaRESUMO
OBJECTIVE: To investigate the relationship between the polymorphism of SG13S114 A/T in the 5-lipoxygenase-activating protein (ALOX5AP) gene and the stability of carotid atherosclerosis. METHODS: Polymorphism of SG13S114 A/T in the ALOX5AP gene was analyzed in 152 cases of acute infarction with stable plaque, and 132 cases of acute infarction with vulnerable plaques, by using polymerase chain reaction and restriction fragment length polymorphism. Carotid artery plaque was analyzed by carotid artery color ultrasound. RESULTS: The frequencies of SG13S114 AA genotype and the A allele in the vulnerable plaque group were higher than that in the stable plaque group (P< 0.01). CONCLUSION: The polymorphism of SG13S114 A/T in the ALOX5AP gene may be associated with the instability of atherosclerosis. And the SG13S114 A allele may be a risk factor of vulnerable plaques.
Assuntos
Doenças das Artérias Carótidas/genética , Proteínas de Transporte/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Proteínas Ativadoras de 5-Lipoxigenase , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
A novel subwavelength surface plasmon polaritons optical filter based on an incompletely directional coupler is proposed and numerically simulated by using the finite difference time domain method with perfectly matched layer absorbing boundary condition. An analytical solution for the resonant condition of the structure is derived by means of the cavity theory. Both analytical and simulative results reveal that the resonant wavelengths are proportional to the length of the slit segment, inversely proportional to the antinode number of a standing wave in the segment, and are related to the slit width and the gap between the two slits. The analytical solution being consistent with the numerical simulation verifies the feasibility of the concept of the new filter structure.
Assuntos
Filtração/instrumentação , Dispositivos Ópticos , Refratometria/instrumentação , Ressonância de Plasmônio de Superfície/instrumentação , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Reprodutibilidade dos Testes , Espalhamento de Radiação , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To investigate the relationship of the polymorphism of SG13S114A/T in ALOX5AP gene with atherosclerotic cerebral infarction (ACI). METHODS: By polymerase chain reaction and restriction fragment length polymorphism, polymorphism of SG13S114A/T in ALOX5AP gene in 412 cases with ACI and 368 non-ACI controls were analyzed. RESULT: There were no statistically significant differences in the ALOX5AP gene SG13S114 AA genotype and A allele frequencies between ACI group and control group (P>0.05). CONCLUSION: The results do not support genotype SG13S114 A allele as the risk gene for ACI.control group.
Assuntos
Proteínas Ativadoras de 5-Lipoxigenase/genética , Infarto Cerebral/genética , Arteriosclerose Intracraniana/genética , Polimorfismo de Fragmento de Restrição , Alelos , Infarto Cerebral/etiologia , Feminino , Genótipo , Humanos , Arteriosclerose Intracraniana/complicações , MasculinoRESUMO
BACKGROUND: Accumulating evidence has suggested that endocan and endoglin may play important roles in cardiovascular disease. However, no previous study has focused on these circulating levels in patients with large-artery atherosclerotic (LAA) stroke. METHODS: Serum levels of endocan and endoglin in 114 patients with LAA stroke and 114 age- and sex-matched controls were measured by ELISA. Serum samples from patients were available on day 1, day 6 and in the 4th week after ischaemic stroke(IS). Stroke severity was determined based on the NIHSS score and the stroke volume. An unfavourable outcome was defined as a mRS score>2 on day 90 after IS. RESULTS: The endocan levels were significantly higher in patients with LAA stroke compared with the controls (p=0.001), and after adjustment for other factors (p=0.001). In addition, higher endocan levels were independently associated with unfavourable outcomes on both day 1 and day 6 after IS (p=0.018 and p=0.011). Endoglin levels were decreased on day 6 (p=0.002) and then recovered in the 4th week after IS. No correlation was found between endocan or endoglin and stroke severity. CONCLUSIONS: Endocan levels are higher in patients with LAA stroke and can help in predicting the short-term unfavourable outcome. Endoglin levels are changed after stroke.
Assuntos
Aterosclerose/sangue , Endoglina/sangue , Proteínas de Neoplasias/sangue , Proteoglicanas/sangue , Acidente Vascular Cerebral/sangue , Idoso , Aterosclerose/complicações , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etiologiaRESUMO
OBJECTIVE: To investigate the expression and significance of matrix metalloproteinase-2 (MMP-2) and MMP-9 in peri-hematoma brain tissues after acute brain hemorrhage in human. METHODS: Forty-two patients with acute brain hemorrhage received surgery, the brain tissues adjacent to hemorrhagic site were obtained during surgery, and positive expressions of MMP-2 and MMP-9 were determined with immunohistochemical staining. Brain tissues from 30 patients with cerebral trauma were obtained to serve as controls. RESULTS: The positive expressions of MMP-2 and MMP-9 in focal brain tissues were significantly elevated in early acute brain hemorrhage. Compared with 28 and 27 cases with MMP-2 and MMP-9 positive expression respectively in control group, there were 39 and 37 cases with MMP-2 and MMP-9 positive expression respectively in acute brain hemorrhage group. There were no significant differences between two groups (both P>0.05). CONCLUSION: MMP-2 and MMP-9 might contribute to brain edema formation in the acute intra-cerebral hemorrhage of human.
Assuntos
Encéfalo/enzimologia , Hemorragia Cerebral/enzimologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of this study was to assess the expression patterns of serum galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-9 (Gal-9), and galectin-3 binding protein (Gal-3BP) and their associations with stroke outcome in large artery atherosclerotic (LAA) stroke. The serum levels of Gal-1, Gal-3, Gal-9, and Gal-3BP were measured by ELISA in 130 patients with LAA stroke and 130 age- and sex-matched controls. Serum samples were collected from the patients on day 1, day 6, and in the 4th week after ischaemic stroke (IS). An unfavourable outcome was defined as a modified Rankin Scale score of >2 on day 90 after IS. Our results indicated that the Gal-3 and Gal-9 levels were higher in patients with LAA stroke than in controls. A higher Gal-3 level was independently associated with an unfavourable outcome both on day 1 and day 6 after IS. In addition, Gal-9 and Gal-1 levels were upregulated on day 6 and in the 4th week after IS, respectively. For Gal-3BP, no difference was detected between patients and controls and no predictive value was found in patients. In conclusion, these findings suggest that the serum levels of Gal-1, Gal-3, and Gal-9 may be associated with LAA stroke.
Assuntos
Aterosclerose/complicações , Galectina 1/sangue , Galectina 3/sangue , Galectinas/sangue , Soro/química , Acidente Vascular Cerebral/patologia , Idoso , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Proteínas de Transporte/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Glicoproteínas/sangue , Humanos , Masculino , PrognósticoAssuntos
Estenose das Carótidas/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/patologia , Adulto , Idoso , Estenose das Carótidas/diagnóstico por imagem , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fitoterapia , UltrassonografiaRESUMO
BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) is a central player in lipid metabolism and atherosclerosis and may thus be involved in ischaemic stroke. However, no study in humans has investigated the association of ANGPTL4 gene polymorphisms or serum levels with ischaemic stroke. METHODS: We investigated the influence of the tagged single nucleotide polymorphisms (tSNPs) rs4076317 (c.207C>G) and rs1044250 (c.797C>T; T266M) of the ANGPTL4 gene on ischaemic stroke risk in a large group of 712 large artery atherosclerotic (LAA) stroke patients and 828 controls. In addition, we examined the association of the serum ANGPTL4 levels with lipid metabolism, LAA stroke severity and ischaemic volume in a sample of 302 LAA stroke patients and 307 controls. RESULTS: The findings reveal that rs4076317 exerts a co-dominant effect on lower serum TG levels compared with common homozygotes. Fewer stroke cases were homozygous for variants of rs4076317 compared with the controls (7.0% vs. 10.9%). The serum ANGPTL4 levels in patients were significantly higher than those in the controls in a univariate manner (P=0.001) and after adjustment for other risk factors (1.463 [1.215-1.835]; P<0.001). Consistently, the ANGPTL4 levels were statistically correlated with higher NIHSS scores (r=0.172, P=0.003) and larger lesion volumes (r=0.124, P=0.031). CONCLUSION: We concluded that the tagged SNPs and high serum levels of ANGPTL4 are associated with LAA stroke and the lipid characteristics.
Assuntos
Angiopoietinas/sangue , Angiopoietinas/genética , Aterosclerose , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral , Idoso , Proteína 4 Semelhante a Angiopoietina , Aterosclerose/sangue , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Aterosclerose/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/genética , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Atherosclerosis (AS) is associated with severe cardiovascular disease. The anti-inflammatory, anti-oxidation, and lipid regulating properties of baicalin suggest potential as an anti-atherosclerotic agent. We therefore investigated whether baicalin can protect against the development of atherosclerosis in an AS rabbit model and explored the underling mechanisms in THP-1 macrophages. METHODS AND RESULTS: In vivo, treatment with baicalin markedly decreased atherosclerotic lesion sizes and lipid accumulation in AS rabbit carotid arteries. Western blotting revealed that the protein expression levels of both peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor alpha (LXRα) were up-regulated in the baicalin group compared with the model group. In vitro, baicalin restricted oxidized-low density lipoprotein (ox-LDL)-induced intracellular lipid accumulation and foam cell formation in THP-1 macrophages. Molecular data showed that baicalin significantly increased the expression levels of PPARγ, LXRα, ATP binding cassette transporters (ABC) A1 and ABCG1. Cell transfection experiments (including PPARγ and LXRα siRNAs) suggested that the effects of baicalin are mediated by the PPARγ-LXRα signalling pathway, which stimulates the expression of ABCA1 and ABCG1. CONCLUSION: These results suggest that baicalin potentially exerts anti-atherosclerosis effects, possibly through the PPARγ-LXRα-ABCA1/ABCG1 pathway, by promoting efflux of cholesterol from macrophages and delaying the formation of foam cells.
Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Aterosclerose/tratamento farmacológico , Colesterol/metabolismo , Flavonoides/uso terapêutico , Receptores X do Fígado/metabolismo , Macrófagos/metabolismo , PPAR gama/metabolismo , Animais , Aterosclerose/sangue , Aterosclerose/metabolismo , Transporte Biológico/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/patologia , Linhagem Celular , Flavonoides/farmacologia , Células Espumosas/efeitos dos fármacos , Células Espumosas/patologia , Humanos , Lipídeos/sangue , Macrófagos/efeitos dos fármacos , Masculino , Modelos Biológicos , RNA Interferente Pequeno/metabolismo , CoelhosRESUMO
BACKGROUND AND AIMS: Sclerostin and Dickkopf-1 (Dkk-1) are potent antagonists of Wnt signalling and might therefore play important roles in cardiovascular disease. We investigated whether serum sclerostin and Dkk-1 levels are associated with acute ischaemic stroke and specific stroke subtypes. METHODS: Serum levels of sclerostin and Dkk-1 were measured by ELISA on day 1 and on day 6 after stroke in 62 patients with large artery atherosclerotic (LAA) stroke, on day 1 after stroke in 62 age- and gender-matched patients with small-artery occlusion (SAO) stroke and on admission in 62 healthy controls. Stroke severity was determined based on the National Institutes of Health Stroke Scale (NIHSS) and by measuring stroke volume on diffusion-weighted imaging. Outcome was measured by the modified Rankin Scale (mRS) on day 90. RESULTS: Compared with controls, serum sclerostin and Dkk-1 levels were significantly higher in both patients with LAA stroke and with SAO stroke, and no difference was detected between the stroke subtypes. Sclerostin and Dkk-1 levels remained stable between the first and sixth day after stroke in the patients with LAA stroke. Receiver operating characteristic curve analysis was used to evaluate sclerostin and Dkk-1 as markers of a high risk of stroke and produced area under curve values of 0.773 and 0.776. Adjusted logistic regression showed that serum sclerostin and Dkk-1 levels remained as independent markers of stroke. No correlations were found between sclerostin or Dkk-1 levels and stroke severity or stroke outcome. CONCLUSIONS: High serum levels of sclerostin and Dkk-1 are associated with acute ischaemic stroke.
Assuntos
Proteínas Morfogenéticas Ósseas/sangue , Isquemia Encefálica/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Acidente Vascular Cerebral/sangue , Doença Aguda , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Área Sob a Curva , Aterosclerose/fisiopatologia , Pressão Sanguínea , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Reprodutibilidade dos Testes , Transdução de Sinais , Fatores de Tempo , Proteínas Wnt/metabolismoRESUMO
Glutamate transporter EAAC1 removes excitatory neurotransmitter in central nervous system, and also absorbs glutamate in epithelia of intestine, kidney, liver and heart for normal cell growth. When a mouse cDNA was screened using EAAC1 cDNA fragment as probe in our lab, a transcript (GenBank U75214) encoding an EAAC1 protein with 148 residues truncated at N-terminal was cloned and named as EAAC2. Sequence analysis shows that EAAC2 has it's own start code and unique 5'UTR that is different from that of EAAC1. A mouse genomic library was screened and a positive clone including EAAC1 CDS was sequenced (GenBank AF 322393) and indicates that normal EAAC1 transcript (GenBank U73521) is transcribed from 10 exons in terms of exon I, II, III, IV, V, VI, VII, VIII, IX, X, and EAAC2 transcript is consisted by exons from IV to IX as same as that of EAAC1 and with its unique exon beta upstream to exon IV and exon delta downstream to IX. EAAC2 transcript has a cluster of transcriptional start sites not overlapping with the transcriptional start sites of EAAC1. These results indicate that EAAC2 is transcribed from an independent promoter but not an alternative splicing event.
Assuntos
Sistema X-AG de Transporte de Aminoácidos/genética , Regiões Promotoras Genéticas , RNA Mensageiro/genética , Simportadores/genética , Transcrição Gênica , Regiões 5' não Traduzidas , Processamento Alternativo , Animais , Animais Recém-Nascidos , Sequência de Bases , Proteínas de Transporte , Elementos de DNA Transponíveis , Transportador 3 de Aminoácido Excitatório , Éxons , Expressão Gênica , Proteínas de Transporte de Glutamato da Membrana Plasmática , Íntrons , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Distribuição TecidualRESUMO
BACKGROUND: Celastrol may have an anti-atherosclerosis effect. This study aimed to investigate if celastrol had an anti-AS effect using a rabbit experimental carotid atherosclerosis model. METHODS: Forty male Japanese white rabbits were divided into the sham group (normal diet), the model group (high fat diet), the group treated with celastrol (high fat diet) and the group treated with atorvastatin (high fat diet) randomly. The rabbits fed a high fat diet underwent balloon injury of the right common carotid artery and were treated with dimethyl sulfoxide (DMSO) (the model group, 3.5 ml/kg/d), celastrol and its dissolvent DMSO (the celastrol group, 1 mg/kg/d and 3.5 ml/kg/d) and atorvastatin and its dissolvent DMSO (the atorvastatin group, 2.5 mg/kg/d and 3.5 ml/kg/d) for 12 weeks by gavage. RESULTS: The ratio of the plaque area and the arterial wall cross-section area in the celastrol group was significantly less than the model group (P < 0.001), and there was no significant difference compared with the atorvastatin group. The serum level of LDL-C of the celastrol group was significantly lower than the model group (P = 0.014), and there was no significant difference compared with the atorvastatin group. The expression of VEGF in the celastrol group was significantly less compared with the model group (P = 0.014), whereas the expression of VEGF in the atorvastatin group and the model group showed no significant differences. CONCLUSION: Our findings suggest that celastrol effectively reduced the plaque ratio, decreased the serum levels of LDL and downregulated the expression of VEGF, suggesting an anti-AS effect of celastrol.