RESUMEN
OBJECTIVE: Our previous study has found that circulating microRNA (miRNA, or miR) -122, -140-3p, -720, -2861, and -3149 are significantly elevated during early stage of acute coronary syndrome (ACS). This study was conducted to determine the origin of these elevated plasma miRNAs in ACS. METHODS: qRT-PCR was performed to detect the expression profiles of these 5 miRNAs in liver, spleen, lung, kidney, brain, skeletal muscles, and heart. To determine their origins, these miRNAs were detected in myocardium of acute myocardial infarction (AMI), and as well in platelets and peripheral blood mononuclear cells (PBMCs, including monocytes, circulating endothelial cells (CECs) and lymphocytes) of the AMI pigs and ACS patients. RESULTS: MiR-122 was specifically expressed in liver, and miR-140-3p, -720, -2861, and -3149 were highly expressed in heart. Compared with the sham pigs, miR-122 was highly expressed in the border zone of the ischemic myocardium in the AMI pigs without ventricular fibrillation (P < 0.01), miR-122 and -720 were decreased in platelets of the AMI pigs, and miR-122, -140-3p, -720, -2861, and -3149 were increased in PBMCs of the AMI pigs (all P < 0.05). Compared with the non-ACS patients, platelets miR-720 was decreased and PBMCs miR-122, -140-3p, -720, -2861, and -3149 were increased in the ACS patients (all P < 0.01). Furthermore, PBMCs miR-122, -720, and -3149 were increased in the AMI patients compared with the unstable angina (UA) patients (all P < 0.05). Further origin identification revealed that the expression levels of miR-122 in CECs and lymphocytes, miR-140-3p and -2861 in monocytes and CECs, miR-720 in monocytes, and miR-3149 in CECs were greatly up-regulated in the ACS patients compared with the non-ACS patients, and were higher as well in the AMI patients than that in the UA patients except for the miR-122 in CECs (all P < 0.05). CONCLUSION: The elevated plasma miR-122, -140-3p, -720, -2861, and -3149 in the ACS patients were mainly originated from CECs and monocytes.
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Síndrome Coronario Agudo/sangre , Leucocitos Mononucleares/metabolismo , MicroARNs/sangre , Síndrome Coronario Agudo/genética , Animales , Perfilación de la Expresión Génica , Humanos , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Porcinos , Porcinos Enanos , Distribución TisularRESUMEN
BACKGROUND: Although the role of fibrinogen as a predictor of acute myocardial infarction (MI) has been well-established, the association of genetic polymorphisms in the fibrinogen gene with MI is still controversial. This study was conducted to elucidate the association between the genetic polymorphisms of the fibrinogen beta-chain (FGB) gene and MI in Chinese Han population. METHODS: The occurrence of 3 common polymorphisms (i.e., -455G/A, R448K and 8558C/G) in a case-control study including 508 patients with MI and 503 healthy controls was investigated. Results Analyses of single polymorphisms showed that individuals carrying the rare alleles for the 3 polymorphisms were significantly associated with a decreased risk of MI. Logistic regression analysis indicated that R448K remained independently associated with MI after adjustment for environmental risk factors (adjusted odds ratio(OR) = 0.71 for KK/RK versus RR, P = 0.023). The three polymorphisms were found to be in strong linkage disequilibrium. Haplotype analyses showed that the A-K-G haplotype (-455A, 448K, 8558G) was associated with a protective effect against MI. Compared with the common haplotype G-R-C, the adjusted OR for A-K-G was 0.68 (95% CI, 0.51-0.90; P = 0.006). CONCLUSION: These data indicate that individuals carrying the FGB 448K allele may be protective against having MI in this population.
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Fibrinógeno/genética , Infarto del Miocardio/genética , Adulto , Anciano , China/etnología , Femenino , Variación Genética , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etiología , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Hydrogen sulfide (H(2)S) plays an important role in the smooth muscle cell relaxation and thereby participates in the development of hypertension. Cystathionine gamma-lyase is the key enzyme in the endogenous production of H(2)S. Up to now, the reports on the relationship between the polymorphisms of cystathionine gamma-lyase gene (CTH) and essential hypertension (EH) are limited. This study was designed to assess their underlying relationship. METHODS: A total of 503 hypertensive patients and 490 age-, gender- and area-matched normotensive controls were enrolled in this study. Based on the FASTSNP, a web server to identify putative functional single nucleotide polymorphisms (SNPs) of genes, we selected two SNPs, rs482843 and rs1021737, in the CTH gene for genotyping. Genotyping was performed by the polymerase chain reaction and restriction fragment length polymorphism method (PCR-RFLP). The frequencies of the alleles and genotypes between cases and controls were compared by the chi-square test. The program Haplo. stats was used to investigate the relationship between the haplotypes and EH. RESULTS: These two SNPs were in Hardy-Weinberg Equilibrium in both cases and controls. The genotype distribution and allele frequencies of them did not significantly differ between cases and controls (all P > 0.05). In the stepwise logistic regression analysis we failed to observe their association with hypertension. In addition, none of the four estimated haplotypes or diplotypes significantly increased or decreased the risk of hypertension before or after adjustment for several known risk factors. CONCLUSIONS: The present study suggests that the SNPs rs482843 and rs1021737 of the CTH gene were not associated with essential hypertension in the Northern Chinese Han population. However, replications in other populations and further functional studies are still necessary to clarify the role of the CTH gene in the pathogenesis of EH.
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Cistationina gamma-Liasa/genética , Hipertensión/genética , Adulto , Anciano , Pueblo Asiatico , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
TNNI3K is a new cardiac-specific MAP kinase whose gene is localized to 1p31.1 and that belongs to a tyrosine kinase-like branch in the kinase tree of the human genome. In the present study we investigated the role of TNNI3K in the cardiac myogenesis process and in the repair of ischemic injury. Pluripotent P19CL6 cells with or without transfection by pcDNA6-TNNI3K plasmid were used to induce differentiation into beating cardiomyocytes. TNNI3K promoted the differentiation process, judging from the increasing beating mass and increased number of alpha-actinin-positive cells. TNNI3K improved cardiac function by enhancing beating frequency and increasing the contractile force and epinephrine response of spontaneous action potentials without an increase of the single-cell size. TNNI3K suppressed phosphorylation of cardiac troponin I, annexin-V(+) cells, Bax protein, and p38/JNK-mediated apoptosis. Intramyocardial administration of TNNI3K-overexpressing P19CL6 cells in mice with myocardial infarction improved cardiac performance and attenuated ventricular remodeling compared with injection of wild-type P19CL6 cells. In conclusion, our study clearly indicates that TNNI3K promotes cardiomyogenesis, enhances cardiac performance, and protects the myocardium from ischemic injury by suppressing p38/JNK-mediated apoptosis. Therefore, modulation of TNNI3K activity would be a useful therapeutic approach for ischemic cardiac disease.
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Diferenciación Celular , Células Madre de Carcinoma Embrionario/enzimología , Quinasas Quinasa Quinasa PAM/metabolismo , Desarrollo de Músculos , Infarto del Miocardio/cirugía , Miocitos Cardíacos/enzimología , Células Madre Pluripotentes/enzimología , Actinina/metabolismo , Potenciales de Acción , Animales , Anexina A5/metabolismo , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Células Madre de Carcinoma Embrionario/patología , Células Madre de Carcinoma Embrionario/trasplante , Epinefrina/metabolismo , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Quinasas Quinasa Quinasa PAM/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Contracción Miocárdica , Infarto del Miocardio/enzimología , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Miocitos Cardíacos/patología , Miocitos Cardíacos/trasplante , Fosforilación , Células Madre Pluripotentes/patología , Células Madre Pluripotentes/trasplante , Proteínas Serina-Treonina Quinasas , Trasplante de Células Madre , Transfección , Troponina I/metabolismo , Función Ventricular Izquierda , Remodelación Ventricular , Proteína X Asociada a bcl-2/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVE: To study the association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population. METHODS: XbaI and EcoRI polymorphisms of the apolipoprotein B (APOB) gene were genotyped by polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) method in 503 unrelated hypertensive patients and 490 healthy controls recruited from international collaborative study of cardiovascular disease in Asia (InterAsia). RESULTS: The difference in the genotypic distributions could be neglected across the groups. The prevalence of X+ allele in healthy controls (4.8%) was less frequent in Chinese, and there was no significant difference in the frequency of the X+ allele between cases (5.7%) and controls (P = 0.38). The observed E- allele frequencies were closely similar among groups (5.9% in cases vs 5.0% in controls, P = 0.39). Logitstic regression analyses revealed that the lack of association still persisted after adjustment of other environmental factors. Haplotype analysis showed that X-E+ was most frequent and no haplotype could significantly contribute to essential hypertension. CONCLUSION: The APOB gene XbaI and EcoRI polymorphisms are not associated with essential hypertension in the Northern Chinese Han population. Future studies on single nucleotide polymorphisms in larger samples are needed to further investigate the possible contribution of the APOB gene to essential hypertension.
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Apolipoproteínas B/genética , Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Hipertensión/genética , Polimorfismo Genético , Estudios de Casos y Controles , China , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In the present study, a yeast two-hybrid screening system was used to identify the interaction partners of cardiac troponin I-interacting kinase (TNNI3K) that might serve as regulators or targets, and thus in turn to gain some insights on the roles of TNNI3K. After screening the adult heart cDNA library with a bait construct encoding the ANK motif of TNNI3K, antioxidant protein 1 (AOP-1) was isolated. The interaction between TNNI3K and AOP-1 was confirmed by the in vitro binding assay and coexpression experiments in vivo. The colocalization of TNNI3K and AOP-1 was clarified by confocal immunofluorescence. Moreover, coexpression of AOP-1 inhibited TNNI3K kinase activity in the in vitro kinase assay.
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Quinasas Quinasa Quinasa PAM/metabolismo , Peroxirredoxinas/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Secuencia de Bases , Línea Celular , Cartilla de ADN/genética , Regulación hacia Abajo , Humanos , Técnicas In Vitro , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Quinasas Quinasa Quinasa PAM/química , Quinasas Quinasa Quinasa PAM/genética , Miocardio/enzimología , Peroxiredoxina III , Peroxirredoxinas/química , Peroxirredoxinas/genética , Dominios y Motivos de Interacción de Proteínas , Mapeo de Interacción de Proteínas , Proteínas Serina-Treonina Quinasas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transfección , Técnicas del Sistema de Dos HíbridosRESUMEN
OBJECTIVE: To analysis plasma homocysteine (Hcy) level and some relative factors in some rheumatological diseases. METHODS: 54 cases with systemic lupus erythematosus (SLE), 48 cases with rheumatoid arthritis (RA), 60 cases with ankylosing spondylitis (AS), 30 cases with undifferentiated spondyloarthropathy (uSpA) and 62 controls were recruited to participate the study. Plasma Hcy, vitamin B(12), folate and the MTHFR gene C677T polymorphism were measured in all patients and controls. RESULTS: (1) Plasma Hcy levels were higher significantly in all disease groups than in the controls, the mean plasma Hcy level was (19.04 +/- 6.86) micromol/L for SLE, (19.07 +/- 7.43) micromol/L for RA, (16.47 +/- 6.50) micromol/L for AS, (16.59 +/- 6.72) micromol/L for uSpA and (12.24 +/- 3.58) micromol/L for controls (P < 0.01). (2) Significant inverse correlation was found between plasma Hcy level and vitamin B(12), folate (r = -0.701, -0.443, respectively; P < 0.01). (3) The MTHFR gene mutation make Hcy level dramatically rise, CC genotype (13.41 +/- 5.78) micromol/L, CT genotype (16.81 +/- 4.22) micromol/L, TT genotype (20.88 +/- 6.60) micromol/L (P < 0.05). TT genotype is susceptible for hyperhomocysteinemia and SLE (OR = 84.46, 7.56 respectively; P < 0.05). CONCLUSIONS: (1) Hyperhomocysteinemia is found in most SLE, RA, AS and uSpA patients. (2) There are lots of factors associated with Hcy concentration, such as folate, vitamin B12 and MTHFR gene mutation. (3) TT genotype of MTHFR is susceptible for hyperhomocysteinemia and SLE.