title: Chlamydophila pneumonia and increased TLR4 gene expression in leukocytes are associated with acute myocardial infarction.
abstract: We investigated the relationship of the positivity for Chlamydophila pneumoniae (Cpn) and Mycoplasma pneumonia (Mpn), inflammatory and metabolic markers, and mRNA expression and polymorphisms of the TLR2, TLR4, IL-6 and TNFA genes with acute myocardial infarction (AMI). Two hundred and eighteen individuals (98 AMI and 120 non-AMI) were selected at two Clinical Centers. Blood samples were drawn to extract DNA and RNA and to measure laboratory variables including anti-Cpn IgM and IgG. Cpn and Mpn genomic DNA as well as TLR2, TLR4, IL-6 and TNFA mRNA expression were evaluated by quantitative real-time PCR (qPCR). Gene polymorphisms were detected by PCR-HRM. AMI patients had higher positivity for Cpn-DNA (17.3%) than non-AMI group (6.7%, p=0.018). In addition, Cpn-DNA positivity was an independent predictor of risk for AMI (OR: 2.56, CI: 1.08 - 6.04, p=0.031). Positivity for anti-Cpn IgG and Mpn-DNA was similar between AMI and non-AMI (> 0.05). TLR4 mRNA expression was higher in AMI than non-AMI individuals (p=0.005). CD14 -260C> T, TNFA -308A> G, TLR2 c.2258G> A, TLR4 c.896A> G and TLR4 c.1196> T variants were not associated with increased risk for AMI (p> 0.05). In the AMI group, individuals carrying CD14 -260CC genotype had higher hsCRP levels than CT/TT carriers (p=0.041). These results are suggestive that Cpn-DNA positivity and increased TLR4 mRNA expression in blood leukocytes may be associated with AMI and could be useful markers to evaluate the severity and progression of the atherosclerotic disease in AMI patients.
authors.affiliation: School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: L G
authors.initials: LG
authors.lastname: Lima-Neto
authors.affiliation: School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: R D C
authors.initials: RD
authors.lastname: Hirata
authors.affiliation: School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: A D
authors.initials: AD
authors.lastname: Luchessi
authors.affiliation: School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: V N
authors.initials: VN
authors.lastname: Silbiger
authors.affiliation: School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: D
authors.initials: D
authors.lastname: Cavichioli
authors.affiliation: Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil.
authors.forename: E S
authors.initials: ES
authors.lastname: Dos Santos
authors.affiliation: Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil.
authors.forename: A G M
authors.initials: AG
authors.lastname: Sousa
authors.affiliation: School of Medical Sciences, Santa Casa of Sao Paulo, Sao Paulo, Brazil.
authors.forename: S R S
authors.initials: SR
authors.lastname: Sprovieri
authors.affiliation: School of Medical Sciences, Santa Casa of Sao Paulo, Sao Paulo, Brazil.
authors.forename: E B
authors.initials: EB
authors.lastname: De Sousa Junior
authors.affiliation: Institute Adolfo Lutz, Sao Paulo, Brazil.
authors.forename: F C P
authors.initials: FC
authors.lastname: Dos Santos
authors.affiliation: Institute Adolfo Lutz, Sao Paulo, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Colombo
authors.affiliation: School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: M H
authors.initials: MH
authors.lastname: Hirata
mesh_terms: D000368:Aged; D061387:Chlamydial Pneumonia / Q000150:complications / Q000378:metabolism*; D016993:Chlamydophila pneumoniae; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009177:Mycoplasma pneumoniae; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism; D011019:Pneumonia, Mycoplasma / Q000150:complications / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012307:Risk Factors; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha