RESUMEN
BACKGROUND: Left ventricular (LV) shape influences LV systolic function. It is possible to assess LV shape using 3-D echocardiography sphericity index (SI). Maintaining mitochondrial DNA copy number (MCN) is important for preserving mitochondrial function and LV systolic function after acute myocardial infarction (AMI). Information is limited, however, regarding the relationship between leukocyte MCN and the subsequent change in LV shape after AMI.MethodsâandâResults:Fifty-five AMI patients undergoing primary angioplasty were recruited. Plasma MCN was measured before primary angioplasty using quantitative polymerase chain reaction. 3-D echocardiography measurement of SI was performed at baseline, and at 1-, 3-, and 6-month follow-up. AMI subjects with MCN lower than the median had a higher 6-month SI and LV volume compared with those with higher MCN. Baseline echocardiographic parameters were similar between the 2 groups. MCN was negatively correlated with 3- and 6-month SI, and 3- and 6-month LV volume. On multiple linear regression analysis, baseline plasma MCN could predict LV SI and LV volume at 6 months after primary angioplasty for AMI, even after adjusting for traditional prognostic factors. CONCLUSIONS: In AMI patients, higher plasma leukocyte MCN at baseline was associated with favorable LV shape and remodeling at 6-month follow-up. Plasma leukocyte MCN may provide a novel prognostic biomarker for LV remodeling after AMI.
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ADN Mitocondrial/genética , Leucocitos , Infarto del Miocardio/fisiopatología , Remodelación Ventricular , Anciano , Angioplastia , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Pronóstico , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: Investigate the latent cytomegalovirus (CMV) infection as a biomarker of oxidative stress and atherosclerosis. METHODS: Latent CMV infection was diagnosed in healthy individuals with PCR-evidence of CMV DNA in peripheral leucocytes. Oxidative stress and atherosclerosis were measured by mitochondrial DNA oxidative damage index (mtDNA(ΔCT)) and intima media thickness (IMT). RESULTS: The CMV DNA positive subjects had a higher mean mtDNA(ΔCT) and greater IMT than subjects in the control group. CONCLUSIONS: Presence of CMV DNA in leucocytes, as a marker of latent CMV infection, was associated with increased levels of oxidative stress and subclinical atherosclerosis in healthy adults.
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Aterosclerosis/sangre , Infecciones por Citomegalovirus/sangre , Citomegalovirus/genética , ADN Viral/sangre , Leucocitos Mononucleares/virología , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/virología , Biomarcadores/sangre , Grosor Intima-Media Carotídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Latencia del VirusRESUMEN
Vascular cytokines, total nitrite, and cyclophilin-A (CyP-A) may be related to the pathogenesis of untreated hypertension. Forty males with normotensive and untreated essential hypertension were recruited in this cytokines survey. Body mass index (BMI), hyperlipidemia, and plasma CyP-A were increased in the hypertensive group (p < 0.05). However, only BMI (p = 0.022) and plasma CyP-A (p = 0.020) were found to be significant contributors to hypertension by multiple regression analysis. CyP-A was also positively correlated with systolic blood pressure (p = 0.029) and diastolic blood pressure (p = 0.047). These findings indicated that plasma CyP-A is a critical molecular biomarker in the early pathogenesis of essential hypertension.
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Biomarcadores/sangre , Ciclofilina A/sangre , Hipertensión/sangre , Presión Sanguínea , Índice de Masa Corporal , Estudios de Casos y Controles , Citocinas/sangre , Humanos , Hiperlipidemias/sangre , Hipertensión/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
Granulocyte colony-stimulating factor (G-CSF) may protect ischemic brain injury either in animal or human. No studies have reported that endogenous G-CSF (enG-CSF) level is related to the severity of ischemic stroke. This study was designed to assess the severity of ischemic patients correlated with the alteration of enG-CSF on the 1st day after an ischemic event. Patient's plasma enG-CSF and scoring of National Institute of Health Stroke Scale were measured on the 1st day after ischemic stroke. The acute ischemic stroke could significantly induce enG-GCF secretion as compared with healthy control group (16.77 vs. 22.86 µg/L, p = 0.001). Elevated enG-CSF concentration was positively correlated with the severity of stroke patients on day 1 after the event (p = 0.006; Spearman correlation coefficient = 0.268). The enG-CSF is a good biomarker for prediction of severity of acute ischemic stroke.
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Isquemia Encefálica/sangre , Factor Estimulante de Colonias de Granulocitos/sangre , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Isquemia Encefálica/patología , Estudios de Casos y Controles , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
BACKGROUND AND PURPOSE: A high plasma concentration of proprotein convertase subtilisin/kexin type 9 is characteristic of a prothrombotic state in cardiovascular diseases. Elevated inflammatory markers, such as interleukin-6, are associated with worse outcomes after ischemic stroke. We aimed to study the role of plasma PCSK9 and IL-6 in acute ischemic stroke with dyslipidemia. METHODS: We divided 123 enrolled patients with first-ever acute ischemic stroke into normotensive and high blood pressure groups and further into high and low pulse pressure subgroups. Clinical characteristics and inflammatory and metabolic parameters, including plasma PCSK9 and IL-6, were recorded. RESULTS: After the analysis of the normotensive and BP groups, there were positive correlations between PP and carotid stenosis (P = 0.031) and plaque numbers (P = 0.013) and between National Institute of Health Stroke Scale scores (P = 0.019) and carotid stenosis severity (P = 0.021) and resistance index (P = 0.04). There was a significant association between plasma cholesterol and PCSK9 (P = 0.044) in the low PP subgroup and IL-6 (P = 0.042) in the high PP subgroup. CONCLUSIONS: Our findings indicated that plasma PCSK9 levels were associated with the low PP subgroup, while IL-6 was associated with the high PP subgroup. Dyslipidemia control is also necessary for those who had a stroke and who have high PP. Further investigation to assess the role of PCSK9 and IL-6 in patients with stroke is required for early treatment and secondary prevention.
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Estenosis Carotídea , Dislipidemias , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Presión Sanguínea , Colesterol , Humanos , Interleucina-6 , Proproteína Convertasa 9 , Accidente Cerebrovascular/metabolismo , SubtilisinasRESUMEN
PURPOSE: Gluten sensitivity (GS) is related to the pathogenesis of sporadic or hereditary ataxia. METHODS: Total of 194 healthy controls and patients with either hereditary ataxia (n=207) or sporadic ataxia (n=361) were tested for the circulating gluten-related autoantibodies which serve as biomarkers to interpret the existence of GS. RESULTS: The incidences of GS in each population were 1% in normal subjects, 2% in hereditary ataxia patients and 9% in sporadic ataxia patients. High serum level of anti-gliadin IgG/IgA and t-transglutaminase IgA were disclosed at the sporadic ataxia patients compared with normal subjects. However, the anti-gliadin IgG is more specific to the disease of sporadic ataxia. CONCLUSION: Relatively higher incidence of GS was found in the population of sporadic ataxia patients but not in either normal subjects or hereditary ataxia patients in Taiwan. Anti-gliadin IgG still is a very powerful indicator to implicate the immune-related sporadic ataxia and we conclude that GS-related sporadic ataxia exists in Taiwan with linkage to autoimmune events.
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Autoanticuerpos/sangre , Ataxia Cerebelosa/inmunología , Gliadina/inmunología , Adulto , Anciano , Ataxia Cerebelosa/epidemiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Incidencia , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Taiwán/epidemiologíaRESUMEN
Cyclophilin A (CypA), secreted from vascular smooth muscle cells and inflammatory cells in response to oxidative stress, promotes vascular atherosclerosis and development of carotid stenosis. Increased concentration of plasma CypA in acute cerebral infarction was demonstrated clinically. The primary aim of this study was to investigate the prognostic impact between CypA level and outcome in patients with acute ischemic stroke. Admission serum CypA concentrations were detected in 66 acute cerebral infarction patients and in 52 healthy individuals. Inflammatory biomarkers, including high-sensitivity C-reactive protein, adhesion molecules, interleukins, and matrix-metalloproteases, were also assessed. We also examined the relationship between plasma biomarkers, blood pressure (BP), pulse pressure, the carotid artery velocity, the prognostic assessment with modified Rankin scale, and stroke recurrence. Plasma CypA concentration was higher on the first day of hospitalization in the high BP stroke group than in normal BP stroke group, which was statistically significant, which was observed even in the third month and sixth month follow-up outpatient periods. For stroke recurrence prediction, there was an important association between the higher (>60) pulse pressure on the seventh day of hospitalization and CypA level on the third month and sixth month follow-up outpatient periods. Our study revealed higher circulating serum levels of CypA in the hypertensive stroke group than in the non-hypertensive stroke group. We expect that elevated plasma CypA level and raised pulse pressure during hospitalization to become valuable biomarkers in predicting stroke recurrence in the sixth month assessment of acute cerebral infarction.
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Infarto Cerebral/sangre , Ciclofilina A/sangre , Anciano , Basigina/sangre , Biomarcadores/sangre , Presión Sanguínea/fisiología , Arterias Carótidas/metabolismo , Arterias Carótidas/patología , Femenino , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Estrés Oxidativo/fisiología , Accidente Cerebrovascular/sangreRESUMEN
Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the ataxin-3 protein that confers a toxic gain of function. Because of the late onset of the disease, we hypothesize that the accumulated oxidative stress or/and defective antioxidant enzyme ability may be contributory factors in the pathogenesis of MJD. In this study, we utilized SK-N-SH and COS7 cells stably transfected with full-length MJD with 78 polyglutamine repeats to examine any alterations in the antioxidant activity. We demonstrated a significant reduction in the ratio of GSH/GSSG and total glutathione content (GSH + 2x GSSG) in mutant MJD cells compared with the wild-type cells under normal or stressful conditions. We also showed that both SK-N-SH-MJD78 and COS7-MJD78-GFP cell lines have lower activities of catalase, glutathione reductase, and superoxide dismutase compared with the wild-type cell lines. In addition, it is known that, when cells are under oxidative stress, the mitochondrial DNA is prone to damage. Our results demonstrated that mitochondrial DNA copy numbers are decreased in mutant cells and SCA3 patients' samples compared with the normal controls. Furthermore, the amount of common mitochondrial DNA 4,977-bp deletion is higher in SCA3 patients compared with that in normal individuals. Overall, mutant ataxin-3 may influence the activity of enzymatic components to remove O(2)(-) and H(2)O(2) efficiently and promote mitochondrial DNA damage or depletion, which leads to dysfunction of mitochondria. Therefore, we suggest that the cell damage caused by greater oxidative stress in SCA3 mutant cells plays an important role, at least in part, in the disease progression.
Asunto(s)
Antioxidantes/metabolismo , Daño del ADN/genética , ADN Mitocondrial/metabolismo , Enfermedad de Machado-Joseph/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Estrés Oxidativo/fisiología , Proteínas Represoras/genética , Adulto , Animales , Ataxina-3 , Encéfalo/metabolismo , Encéfalo/fisiopatología , Células COS , Línea Celular Tumoral , Chlorocebus aethiops , ADN Mitocondrial/genética , Metabolismo Energético/genética , Femenino , Dosificación de Gen/genética , Humanos , Enfermedad de Machado-Joseph/genética , Enfermedad de Machado-Joseph/fisiopatología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Mutación/genética , Regulación hacia Arriba/fisiologíaRESUMEN
BACKGROUND: Hyperhomocysteinemia is an independent risk factor for cardiovascular events. The T allele of 677 C/T polymorphism at the methylenetetrahydrofolate reductase (MTHFR) gene has been reported to induce mild hyperhomocysteinemia. In the present study, we investigated the relationship between this polymorphism and adhesion molecules and total nitric oxide (NOx). METHODS: The adhesion molecules tested in the present study were soluble E-selectin (sE-selectin), vascular adhesion molecule (sVCAM), and intercellular adhesion molecule (sICAM). A total of 297 subjects had data on these atherosclerotic biomarkers and the MTHFR genotypes. The genetic effect was estimated in the multivariate regression models with adjustment of covariates. Homocysteine, folate, vitamin B6 and vitamin B12 levels were measured in 181 subjects for the test of association between the biomarkers and homocysteine levels. RESULTS: The genotype distribution was in Hardy-Weinberg equilibrium. The sVCAM levels increased with the number of the T allele, while the NOx levels decreased with the number of the T allele. We found that the T allele was significantly associated with high sVCAM levels (p=0.002) and low NOx levels (p=0.011) in the regression models. The MTHFR genotypes were associated with homocysteine levels (p=0.031). Mild hyperhomocysteinemia (>12 micromol/L) was significantly associated with sVCAM levels (p=0.036). The NOx levels were lower in the hyperhomocysteinemia group than in the normal homocysteine group, but the difference was not significant. The genotypes were not significantly associated with either sE-selectin or sICAM. CONCLUSIONS: The detrimental T allele exerted an additive effect to increase sVCAM and decrease NOx concentrations, which may contribute to atherosclerosis.
Asunto(s)
Moléculas de Adhesión Celular/sangre , Selectina E/sangre , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Óxido Nítrico/sangre , Polimorfismo Genético , Molécula 1 de Adhesión Celular Vascular/sangre , Adulto , Anciano , Femenino , Homocisteína/sangre , Humanos , Masculino , Persona de Mediana Edad , Vitamina B 12/sangre , Vitamina B 6/sangreRESUMEN
To find the associations of circulating cyclophilin A (CyP A) and CD147/EMMPRIN with renal outcomes in type 2 diabetes patients and possible pathogenesis involved. Total 131 patients were recruited since 2004. Glycated hemoglobin, blood glucose and urine albumin-creatinine ratio levels at baseline and every 3 months were measured. Plasma CyP A and CD147 were also measured at baseline. Patients were divided into two groups based upon the median level of the baseline plasma CyP A value: < 93.64 ng/mL (group A, n = 65), ≥ 93.64 ng/mL (group B, n = 66). The estimated glomerular filtration rate was calculated at each follow-up visit. Besides, mitochondrial function assay by cellular mitochondrial energy utility was studied when cells were exposed to glucose or exogenous CyP A or both. Multivariate analysis, using median level (93.64) ng/mL as the cut-off value, revealed that circulating CyP A and CD147 levels at baseline were associated with the baseline estimated glomerular filtration rate (eGFR) (p = .042 and p = .001 separately) in cross-sectional analysis. Longitudinally, higher baseline plasma CyP A level was also correlated to a rapid decline in eGFR (p = .016). The results were also significant when using the continuous plasma CyP A level (p = .003). In cells exposed to glucose, results of oxygen consumption rate (OCR) showed a significant reduction in basal respiration, maximal respiration and ATP production. Depressed OCR further occurred when incubated with both of CyP A and glucose. Plasma CyP A and CD147 can serve as indicators of renal disease progression in type 2 diabetes patients.
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Basigina/sangre , Ciclofilina A/sangre , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/patología , Progresión de la Enfermedad , Anciano , Animales , Glucemia/análisis , Células Cultivadas , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/metabolismo , Femenino , Humanos , Estudios Longitudinales , Masculino , Ratones , Ratones Transgénicos , Mitocondrias/metabolismoRESUMEN
BACKGROUND: Cyclophilin A plays a pathogenic role in the development and progression of atherosclerosis, which can be assessed by measuring carotid intima-media thickness. The primary aim of this study was to examine the interaction between plasma Cyclophilin A level and carotid intima-media thickness in patients with acute ischemic stroke. METHOD: Plasma concentration of Cyclophilin A was measured on admission in 66 consecutive patients who had been hospitalized for acute cerebral stroke and in 52 case-control subjects without a history of acute stroke. Subjects in both groups also underwent ultrasound B-mode imaging to measure the mean and maximum intima-media thickness of the carotid artery. Inflammatory biomarkers including high-sensitivity C-reactive protein and fibrinogen were also assessed. RESULTS: We found that the plasma concentration of Cyclophilin A was significantly higher in patients with acute ischemic stroke (p = 0.042). Increased Cyclophilin A was also correlated with carotid intima-media thickness in the patient group (p < 0.001). Among the risk factors for cerebral stroke examined in this study, only hypertension was significantly associated with plasma Cyclophilin A level. CONCLUSION: Increased plasma Cyclophilin A levels might be involved in the pathophysiology of acute ischemic stroke and Cyclophilin A might serve as a biomarker in risk assessment of acute stroke patients.
Asunto(s)
Biomarcadores/sangre , Isquemia Encefálica/complicaciones , Ciclofilina A/sangre , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/etiología , Adulto , Anciano , Análisis de Varianza , Proteína C-Reactiva/metabolismo , Arteria Carótida Común/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Femenino , Humanos , Hipertensión/etiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Accidente Cerebrovascular/complicacionesRESUMEN
Exogenous administration of coenzyme Q10 (CoQ10) has been shown in experimental models to have a protective effect against ischemia-reperfusion injury. However, it is unclear whether follow-up plasma CoQ10 concentration is prognostic of left ventricular (LV) performance after primary balloon angioplasty in patients with acute ST segment elevation myocardial infarction (STEMI).We prospectively recruited 55 patients with STEMI who were treated with primary coronary balloon angioplasty. Plasma CoQ10 concentrations were measured before primary angioplasty (baseline) and 3 days, 7 days, and 1 month after STEMI using high-performance liquid chromatography. Echocardiography was performed at baseline and at 6-month follow-up. The control group comprised 54 healthy age- and sex-matched volunteers.Serial circulating CoQ10 concentrations significantly decreased with time in the STEMI group. The LV ejection fraction at 6-month follow-up positively correlated with the 1-month plasma CoQ10 tertile. Higher plasma CoQ10 concentrations at 1 month were associated with favorable LV remodeling and systolic function 6 months after STEMI. Multiple linear regression analysis showed that changes in CoQ10 concentrations at 1-month follow-up were predictive of LV systolic function 6 months after STEMI. Changes in CoQ10 concentrations correlated negatively with baseline oxidized low-density lipoprotein and fibrinogen concentrations and correlated positively with leukocyte mitochondrial copy number at baseline.Patients with STEMI who had higher plasma CoQ10 concentrations 1 month after primary angioplasty had better LV performance at 6-month follow-up. In addition, higher plasma CoQ10 concentration was associated with lower grade inflammatory and oxidative stress status. Therefore, plasma CoQ10 concentration may serve as a novel prognostic biomarker of LV systolic function after revascularization therapy for acute myocardial infarction.
Asunto(s)
Angioplastia Coronaria con Balón , Infarto del Miocardio con Elevación del ST/terapia , Volumen Sistólico , Ubiquinona/análogos & derivados , Función Ventricular Izquierda , Biomarcadores/sangre , Estudios de Casos y Controles , Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Femenino , Fibrinógeno/análisis , Estudios de Seguimiento , Humanos , Leucocitos/metabolismo , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Ubiquinona/sangre , Remodelación VentricularRESUMEN
Cyclophilin A (CyPA), an oxidative stress-induced factor, was found to play an important role in the aneurysm formation. Our working hypothesis was that the plasma level of CyPA in ruptured intracranial aneurysm could predict the neurological outcome. From 2011 to 2013, a total of 36 patients with ruptured saccular intracranial aneurysm were recruited in our study. Before coil embolization, we draw blood samples at the orifice of a culprit aneurysm and in the remote peripheral vein for measurements of the CyPA levels. We utilized the modified Rankin scale 30 days after aneurysm rupture as the outcome measure. Generalized linear models were used to estimate the adjusted odds ratios of the poor neurological outcome given the presence of high plasma level of CyPA. The aneurysmal and venous CyPA levels were significantly associated with the initial clinical severity (P = 0.004 and 0.03, respectively) and 30-day outcome (P = 0.01 and 0.02, respectively). The aneurysmal CyPA levels modestly correlated with age and high Fisher grade (ρ = 0.39 and 0.41; P = 0.02 and 0.01, respectively). The aneurysmal CyPA levels strongly correlated with the venous counterpart (ρ = 0.89; P < 0.001). Patients with high levels of aneurysmal CyPA were 15.66 times (95% CI, 1.48-166.24; P = 0.02) more likely to have worse neurological outcome than those with the low levels after adjustment of the age, gender, and the documented confounding factors. High plasma level of CyPA is a significant prognostic biomarker for poor neurological outcome in patients with ruptured intracranial aneurysm.
Asunto(s)
Aneurisma Roto/sangre , Aneurisma Roto/terapia , Ciclofilina A/sangre , Aneurisma Intracraneal/sangre , Aneurisma Intracraneal/terapia , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma Roto/diagnóstico , Biomarcadores/sangre , Embolización Terapéutica , Femenino , Humanos , Aneurisma Intracraneal/diagnóstico , Modelos Lineales , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Interleukin-6 (IL-6), a proinflammatory cytokine, was found to surge in the cerebral spinal fluid after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that the plasma level of IL-6 could be an independent biomarker in predicting clinical outcome of patients with ruptured intracranial aneurysm. METHODS: We prospectively included 53 consecutive patients treated with platinum coil embolization of the ruptured intracranial aneurysm. Plasma IL-6 levels were measured in the blood samples at the orifices of the aneurysms and from peripheral veins. The outcome measure was the modified Rankin Scale one month after SAH. Multiple logistic regression analyses were used to evaluate the associations between the plasma IL-6 levels and the neurological outcome. RESULTS: Significant risk factors for the poor outcome were old age, low Glasgow Coma Scale (GCS) on day 0, high Fisher grades, and high aneurysmal and venous IL-6 levels in univariate analyses. Aneurysmal IL-6 levels showed modest to moderate correlations with GCS on day 0, vasospasm grade and Fisher grade. A strong correlation was found between the aneurysmal and the corresponding venous IL-6 levels (ρ = 0.721; P<0.001). In the multiple logistic regression models, the poor 30-day mRS was significantly associated with high aneurysmal IL-6 level (OR, 17.97; 95% CI, 1.51-214.33; P = 0.022) and marginally associated with high venous IL-6 level (OR, 12.71; 95% CI, 0.90-180.35; P = 0.022) after adjusting for dichotomized age, GCS on day 0, and vasospasm and Fisher grades. CONCLUSIONS: The plasma level of IL-6 is an independent prognostic biomarker that could be used to aid in the identification of patients at high-risk of poor neurological outcome after rupture of the intracranial aneurysm.
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Aneurisma Roto/diagnóstico , Interleucina-6/sangre , Aneurisma Intracraneal/diagnóstico , Adulto , Anciano , Aneurisma Roto/patología , Aneurisma Roto/terapia , Área Bajo la Curva , Biomarcadores/sangre , Embolización Terapéutica , Femenino , Escala de Coma de Glasgow , Humanos , Interleucina-6/líquido cefalorraquídeo , Aneurisma Intracraneal/patología , Aneurisma Intracraneal/terapia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Estudios Prospectivos , Curva ROC , Factores de Riesgo , Hemorragia Subaracnoidea/etiología , Hemorragia Subaracnoidea/patologíaRESUMEN
BACKGROUND: Cyclophilin A (CyPA) concentration increases in acute coronary syndrome. In an animal model of acute myocardial infarction, administration of angiotensin-converting-enzyme inhibitor was associated with lower left ventricular (LV) CyPA concentration and improved LV performance. This study investigated the relationships between changes in plasma CyPA concentrations and LV remodeling in patients with ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: We enrolled 55 patients who underwent percutaneous coronary intervention for acute STEMI. Plasma CyPA, matrix metalloproteinase (MMP), interleukin-6 and high-sensitivity C-reactive protein concentrations were measured at baseline and at one-month follow-up. Echocardiography was performed at baseline and at one-, three-, and six-month follow-up. Patients with a decrease in baseline CyPA concentration at one-month follow-up (n = 28) had a significant increase in LV ejection fraction (LVEF) (from 60.2 ± 11.5% to 64.6 ± 9.9%, p < 0. 001) and preserved LV synchrony at six months. Patients without a decrease in CyPA concentration at one month (n = 27) did not show improvement in LVEF and had a significantly increased systolic dyssynchrony index (SDI) (from 1.170 ± 0.510% to 1.637 ± 1.299%, p = 0.042) at six months. Multiple linear regression analysis showed a significant association between one-month CyPA concentration and six-month LVEF. The one-month MMP-2 concentration was positively correlated with one-month CyPA concentration and LV SDI. Conclusions : Decreased CyPA concentration at one-month follow-up after STEMI was associated with better LVEF and SDI at six months. Changes in CyPA, therefore, may be a prognosticator of patient outcome.
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Ciclofilina A/sangre , Infarto del Miocardio/sangre , Remodelación Ventricular/fisiología , Área Bajo la Curva , Proteína C-Reactiva/metabolismo , Ecocardiografía , Humanos , Interleucina-6/sangre , Metaloproteinasas de la Matriz/sangre , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea/métodos , Proyectos Piloto , Pronóstico , Estudios Prospectivos , Taiwán , Factores de Tiempo , Función Ventricular Izquierda/fisiologíaRESUMEN
The effects of long-term smoking on mitochondrial DNA (mtDNA) deletions in hair follicles were investigated in subjects with different antioxidant capacity. Twenty-two male smokers with a smoking index of greater than 5 pack-years and without any known systemic diseases were recruited for this study. Forty healthy nonsmoking males were included as controls. We found that the concentrations of ascorbate and alpha-tocopherol and the activities of glutathione S-transferase (GST) and glutathione peroxidase in blood plasma were significantly decreased in smokers. The levels of glutathione and protein thiols in whole blood and the incidence of a 4,977 bp deletion of mtDNA (dmtDNA) in hair follicles were significantly increased in smokers. A significantly higher incidence of the 4,977 bp dmtDNA was found in smokers with plasma GST activity less than 5.66 U/l (OR = 7.2, P = 0.020). Using multiple covariate ANOVA and logistic regression, we found that age and low plasma GST activity were the only two risk factors for the 4,977 bp dmtDNA. These results suggest that smoking depletes antioxidants and causes mtDNA deletions and that plasma GST may play an important role in the preservation of the mitochondrial genome in tissue cells of smokers.
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Antioxidantes/metabolismo , ADN Mitocondrial/genética , Folículo Piloso/patología , Mutación , Fumar/efectos adversos , Anciano , Análisis de Varianza , Ácido Ascórbico/sangre , Estudios de Casos y Controles , Eliminación de Gen , Glutatión Transferasa/sangre , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Análisis de Regresión , Factores de Tiempo , alfa-Tocoferol/sangreRESUMEN
The role of oxidative stress in the regulation of the copy number of mitochondrial DNA (mtDNA) in human leukocytes is unclear. In this study, we investigated the redox factors in plasma that may contribute to the alteration of mtDNA copy number in human leukocytes. A total of 156 healthy subjects of 25-80 years of age who exhibited no significant difference in the distribution of subpopulations of leukocytes in blood were recruited. Small-molecular-weight antioxidants and thiobarbituric acid reactive substances (TBARS) in plasma and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4,977bp deletion of mtDNA in leukocytes were determined. The mtDNA copy number in leukocytes was determined by real-time PCR. The results showed that the copy number of mtDNA in leukocytes was changed with age in a biphasic manner that fits in a positively quadratic regression model (P = 0.001). Retinol (P = 0.005), non-protein thiols (P = 0.001) and ferritin (P = 0.004) in plasma and total glutathione in erythrocytes (P = 0.046) were the significant redox factors that correlated with the mtDNA copy number in leukocytes in a positive manner. By contrast, alpha-tocopherol levels in plasma (P = 0.001) and erythrocytes (P = 0.033) were negatively correlated with the mtDNA copy number in leukocytes. Three oxidative indices including the incidence of 4,977 bp deletion of mtDNA (P = 0.016) and 8-OHdG content in leukocytes (P = 0.003) and TBARS in plasma (P = 0.001) were all positively correlated with the copy number of mtDNA in leukocytes. Taken these findings together, we suggest that the copy number of mtDNA in leukocytes is affected by oxidative stress in blood circulation elicited by the alteration of plasma antioxidants/prooxidants and oxidative damage to DNA.
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ADN Mitocondrial/genética , Desoxiguanosina/análogos & derivados , Dosificación de Gen , Leucocitos/metabolismo , Estrés Oxidativo , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Anciano , Anciano de 80 o más Años , Antioxidantes/metabolismo , Daño del ADN , ADN Mitocondrial/metabolismo , Desoxiguanosina/metabolismo , Eritrocitos/metabolismo , Femenino , Ferritinas/sangre , Glutatión/metabolismo , Homocisteína/sangre , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Compuestos de Sulfhidrilo/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Vitamina A/sangreRESUMEN
Many uncertain and inconsistent etiologies of cerebral aneurysmal rupture including a wide spectrum of factors have been reported. Our recent observation discloses the potential new factor of cerebral aneurysm rupture with cerebral venous pressure gradient. We retrospectively reviewed 52 cases treated with coil embolization with or without cerebral aneurysmal rupture. Seventeen males and 30 females were recruited in this study. Quantitative color-coded cerebral angiography was performed during coil therapeutic procedures to measure cerebral venous circulation. Ruptured cases had shorter and symmetrical cerebral venous circulation time (P <0.05). In addition, an asymmetrical venous outflow pattern was critical for aneurysmal rupture. Non-ruptured cases tended to have slower and asymmetrical cerebral venous circulation compared with rupture cases. Symmetrical and shorter cerebral venous circulation in the dysplasia venous outlet may be a potential new factor for cerebral aneurysm rupture.
Asunto(s)
Aneurisma Roto/fisiopatología , Circulación Cerebrovascular/fisiología , Hemodinámica/fisiología , Aneurisma Intracraneal/fisiopatología , Adolescente , Anciano , Aneurisma Roto/etiología , Angiografía Cerebral , Embolización Terapéutica/métodos , Femenino , Humanos , Aneurisma Intracraneal/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Anemia is associated with high mortality and poor prognosis after acute coronary syndrome (ACS). Increased red cell distribution width (RDW) is a strong independent predictor for adverse outcomes in ACS. The common underlying mechanism for anemia and increased RDW value is iron deficiency. It is not clear whether serum iron deficiency without anemia affects left ventricular (LV) performance after primary angioplasty for acute myocardial infarction (AMI). We investigated the prognostic value of serum iron concentration on LV ejection fraction (EF) at 6 months and its relationship to thrombolysis in myocardial infarction (TIMI) risk score in post MI patients. METHODS: We recruited 55 patients who were scheduled to undergo primary coronary balloon angioplasty after AMI and 54 age- and sex-matched volunteers. Serum iron concentration and interleukin-6 levels were measured before primary angioplasty. LVEF was measured by echocardiography at baseline and after 6 months. TIMI risk score was calculated for risk stratification. RESULTS: Serum iron concentration was significantly lower in those in whom LVEF had not improved ≥ 10% from baseline (52.7 ± 24.1 versus 80.8 ± 50.8 µg/dl, P = 0.016) regardless of hemoglobin level, and was significantly lower in the AMI group than in the control group (62.5 ± 37.7 versus 103.0 ± 38.1 µg/dl, P<0.001). Trend analysis revealed that serum iron concentration decreased as TIMI risk score increased (P = 0.002). In addition, lower serum iron concentrations were associated with higher levels of inflammatory markers. Multiple linear regression showed that baseline serum iron concentration can predict LV systolic function 6 months after primary angioplasty for AMI even after adjusting for traditional prognostic factors. CONCLUSION: Hypoferremia is not only a marker of inflammation but also a potential prognostic factor for LV systolic function after revascularization therapy for AMI, and may be a novel biomarker for therapeutic intervention.
Asunto(s)
Síndrome Coronario Agudo , Angioplastia Coronaria con Balón , Ventrículos Cardíacos/fisiopatología , Hierro/sangre , Infarto del Miocardio , Volumen Sistólico , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/fisiopatología , Síndrome Coronario Agudo/cirugía , Adulto , Anciano , Biomarcadores/sangre , Femenino , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/cirugía , Estudios ProspectivosRESUMEN
OBJECTIVES: Oxidized low-density lipoproteins (oxLDL) and oxidized low-density lipoprotein autoantibodies (OLAB) have been detected in human plasma and atherosclerotic lesions. OLAB appear to play a role in the clearance of oxLDL from circulation. Higher levels of OLAB appear to be associated with a reduced risk of a wide range of cardiovascular diseases. We investigated the prognostic value of plasma oxLDL and OLAB in patients undergoing primary coronary balloon angioplasty for acute ST-elevation myocardial infarction (STEMI). METHODS: Plasma oxLDL and OLAB concentrations were measured in 56 patients with acute STEMI before primary angioplasty, and then 3 days, 7 days and 1 month after the acute event. Follow-up angiography was repeated 6 months later to detect the presence of restensosis (defined as >50% luminal diameter stenosis). The thrombolysis in myocardial infarction (TIMI) risk score was calculated to determine the relationship between OLAB/oxLDL ratio and TIMI risk scores. RESULTS: Of the 56 patients, 18 (31%) had angiographic evidence of restenosis. Plasma OLAB concentrations were significantly lower in the restenosis group before angioplasty (181±114 vs. 335±257 U/L, pâ=â0.003), and at day 3 (155±92 vs. 277±185 U/L, p<0.001) and day 7 (177±110 vs. 352±279 U/L, p<0.001) after the acute event. There was no difference in oxLDL concentration between the two groups. The ratio of OLAB/oxLDL positively correlated with TIMI risk scores before angioplasty (p for trend analysis, pâ=â0.004), at day 3 (pâ=â0.008) and day 7 (p<0.001) after STEMI. SIGNIFICANCE: A relative deficit of OLAB, and hence likely impaired clearance of oxLDL, is associated with the risk of arterial restenosis after primary angioplasty for acute STEMI.