RESUMO
BACKGROUND AND PURPOSE: Ischemic stroke provokes a systemic inflammatory response. The purpose of this study was to characterize this response on the gene expression level in circulating mononuclear leukocytes from acute ischemic stroke (AIS) patients. METHODS: RNA from peripheral blood mononuclear cells (PBMCs) of AIS patients (24 + 2 hours after onset of symptoms) was analyzed with Affymetrix U133A GeneChips using a pooled design. We compared the gene expression signature from AIS patients (n = 20), stroke survivors (n = 15), patients with acute traumatic brain injury (ATBI, n = 15) and healthy control subjects without vascular risk factors (n = 15). RESULTS: Expression levels of 9682 probe sets with present calls on each GeneChip were compared. Between AIS patients and stroke survivors or between AIS patients and ATBI patients there were no significant differences in expression values of single genes after correction for multiple testing. However, comparison of the PBMC expression profiles from AIS patients and healthy subjects revealed significantly different expression (p = 0.012) of a single probe set, specific for phosphodiesterase 4 D (PDE4D). In order to detect modest expression differences in multiple genes with a presumed cumulative effect we studied the gene expression of functional groups of genes by global statistical tests. Analysis of 11 gene groups revealed differential expression between AIS patients and healthy subjects for genes involved in the inflammatory response (GeneOntology GO:0006954). Genes encoding the N-formyl peptide receptor-like 1 (FPRL1), interleukin-1 receptor antagonist (IL1RN) and complement component 3a receptor 1 (C3AR1) contributed most to the observed difference. CONCLUSIONS: This transcriptome analysis did not identify significant changes between circulating mononuclear cells from AIS patients 24 hours after stroke and closely matched stroke survivors. However, comparing AIS patients with healthy control subjects revealed measurable differences in PDE4D and in inflammatory response genes when considered as a set.
Assuntos
Isquemia Encefálica/genética , Expressão Gênica/genética , Leucócitos Mononucleares/metabolismo , Acidente Vascular Cerebral/genética , Doença Aguda , Idoso , Isquemia Encefálica/sangue , Isquemia Encefálica/fisiopatologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Feminino , Perfilação da Expressão Gênica , Marcadores Genéticos/genética , Humanos , Inflamação/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Receptores de Complemento/genética , Receptores de Formil Peptídeo/genética , Receptores de Lipoxinas/genética , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/fisiopatologiaAssuntos
Anormalidades Múltiplas/genética , Anormalidades do Olho/genética , Sindactilia/genética , Anormalidades Dentárias/genética , Adolescente , Criança , Pré-Escolar , Conexina 43/genética , Feminino , Dedos/anormalidades , Junções Comunicantes/genética , Genes Dominantes , Humanos , Pessoa de Meia-Idade , Mutação , Fenótipo , Dedos do Pé/anormalidadesRESUMO
The methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism was studied in 174 German patients with cervical artery dissection (CAD). The results were compared with published data on 927 healthy German controls. In the series of patients, the frequency of T alleles and of TT carriers was slightly higher (13.8%) than among the healthy controls (10.6%). In patients with multiple dissections (n = 50), the proportion of TT carriers (18%) was found to be even higher and correlated with the number of events. The MTHFR C677T polymorphism was suggested to modify the risk for CAD.
Assuntos
Dissecção Aórtica/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Artérias/patologia , Estudos de Casos e Controles , Genótipo , Alemanha , Humanos , Pescoço/irrigação sanguínea , Polimorfismo Genético , Fatores de RiscoRESUMO
Although the function and effects of many growth factors and extracellular matrix (ECM) molecules have been described for several periodontal tissues in vivo and in vitro, the molecular interactions involved in the communication between cells of the periodontal ligament and the alveolar bone are poorly understood. To contribute to the identification of such interactions, we have generated co-cultures (CCs) of periodontal ligament fibroblasts (PDLs) and alveolar bone cells (ABCs) and compared mRNA expression for various growth factors, ECM molecules, and matrix metalloproteinase13 (MMP13) after 1 and 2 weeks with matched mono-cultures (MCs) by reverse transcription/polymerase chain reaction. Compared with CCs of 1 week, PDLs and ABCs after 2 weeks revealed relatively high levels of all analyzed mRNAs, viz., for EGF, HGF, VEGF, TGFbeta1, collagen-I (COL1), osteonectin (ON), fibronectin (FN1), and MMP13. At week 2, when compared with MCs, CCs showed an elevation of all tested mRNAs in PDLs and ABCs, except for TGFbeta1 and FN1, which only increased in PDLs. After 1 week, when CCs were compared with MCs, mRNAs for HGF and TGFbeta1 were less abundant in PDLs and ABCs, whereas the other genes exhibited lower expression levels in only one of the cell types. Analysis of our data indicated that the expression of mRNAs for growth factors and for COL1, ON, FN1, and MMP13 was modulated in the distinct cell types with respect to culture time and culture type. The differences in the mRNA expression patterns between CCs and MCs suggest that the respective genes are involved in the molecular interactions of PDLs and ABCs.
