6 results on '"Levula, Mari"'
Search Results
2. miR-21, miR-210, miR-34a, and miR-146a/b are up-regulated in human atherosclerotic plaques in the Tampere Vascular Study
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Raitoharju, Emma, Lyytikäinen, Leo-Pekka, Levula, Mari, Oksala, Niku, Mennander, Ari, Tarkka, Matti, Klopp, Norman, Illig, Thomas, Kähönen, Mika, Karhunen, Pekka J., Laaksonen, Reijo, and Lehtimäki, Terho
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ATHEROSCLEROTIC plaque , *GENETIC regulation , *NON-coding RNA , *GENE expression , *GENE targeting , *MESSENGER RNA - Abstract
Abstract: Objective: MicroRNAs are small non-coding RNAs that inversely regulate their target gene expression. The whole miRNA profile of human atherosclerotic plaques has not been studied previously. The aim of this study was to investigate the miRNA expression profile in human atherosclerotic plaques as compared to non-atherosclerotic left internal thoracic arteries (LITA), and to connect this expression to the processes in atherosclerosis. Methods: The miRNA expression profiles of six LITAs and 12 atherosclerotic plaques obtained from aortic, carotid, and femoral atherosclerotic arteries from Tampere Vascular Study were analyzed. The analyses were performed with Agilent''s miRNA Microarray. The expression levels of over 4-fold up-regulated miRNAs were verified with qRT-PCR from a larger population (n =50). Messenger RNA levels were analyzed with Illumina''s Expression BeadChip to study miRNA target expression. Results: Ten miRNAs were found to be differently expressed in atherosclerotic plaques when compared to controls (p <0.05). The expression of miR-21, -34a, -146a, -146b-5p, and -210 was verified and found to be significantly up-regulated in atherosclerotic arteries versus LITAs (p <0.001, fold changes 4.61, 2.55, 2.87, 2.82, and 3.92, respectively). Several predicted targets of these miRNAs were down-regulated, and gene set enrichment analysis showed several pathways which could be differently expressed due to this miRNA profile. Conclusions: The microRNA expression profile differs significantly between atherosclerotic plaques and control arteries. The most up-regulated miRNAs are involved in processes known to be connected to atherosclerosis. Interfering with the miRNA expression in the artery wall is a potential way to affect atherosclerotic plaque and cardiovascular disease development. [Copyright &y& Elsevier]
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- 2011
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3. Common variation in the ADAM8 gene affects serum sADAM8 concentrations and the risk of myocardial infarction in two independent cohorts
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Raitoharju, Emma, Seppälä, Ilkka, Levula, Mari, Kuukasjärvi, Pekka, Laurikka, Jari, Nikus, Kjell, Huovila, Ari-Pekka J., Oksala, Niku, Klopp, Norman, Illig, Thomas, Laaksonen, Reijo, Karhunen, Pekka J., Viik, Jari, Lehtinen, Rami, Pelto-Huikko, Markku, Tarkka, Matti, Kähönen, Mika, and Lehtimäki, Terho
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MYOCARDIAL infarction risk factors , *GENETIC polymorphisms , *METALLOPROTEINASES , *ANGIOGRAPHY , *ATHEROSCLEROTIC plaque , *COHORT analysis , *ENZYME-linked immunosorbent assay - Abstract
Abstract: Objective: The single nucleotide polymorphism (SNP) rs2995300 in the metalloproteinase-disintegrin gene ADAM8 has been shown to affect the areas of complicated coronary plaques and the risk of fatal myocardial infarction (MI) in men. This study was set up to further investigate the role of ADAM8 in MI. Aim: To investigate the possible association of the ADAM8 SNPs rs2995300 and rs2275725 with ADAM8 mRNA levels, serum soluble ADAM8 (sADAM8) concentrations, and MI risk. Methods: Samples from the Finnish cardiovascular study (FINCAVAS, N =2156) and the angiography and genes study (ANGES, N =1000) were genotyped. Serum sADAM8 concentrations were determined with ELISA (N =443). ADAM8 mRNA levels in atherosclerotic plaques were analysed from the tampere vascular study (TVS, N =53) samples. Results: A significantly increased MI risk for carriers of the rs2995300C allele and the rs2275725 A allele was revealed in the meta-analysis of the ANGES and FINCAVAS patient data (OR=1.42, P <0.001 and OR=1.43, P <0.001). The risk increase was comparable to that caused by smoking in these cohorts. The risk allele carriers also had higher sADAM8 serum concentrations. Conclusions: The risk alleles of the investigated ADAM8 SNPs were associated with elevated sADAM8 serum levels and MI risk. The present results implicate ADAM8 in the development of CVDs and suggest its prognostic and therapeutic potential. [Copyright &y& Elsevier]
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- 2011
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4. Kindlin 3 (FERMT3) is associated with unstable atherosclerotic plaques, anti-inflammatory type II macrophages and upregulation of beta-2 integrins in all major arterial beds.
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Oksala, Niku, Pärssinen, Jenita, Seppälä, Ilkka, Klopp, Norman, Illig, Thomas, Laaksonen, Reijo, Levula, Mari, Raitoharju, Emma, Kholova, Ivana, Sioris, Thanos, Kähönen, Mika, Lehtimäki, Terho, and Hytönen, Vesa P.
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ATHEROSCLEROTIC plaque , *KINDLING (Neurology) , *ANTI-inflammatory agents , *MACROPHAGES , *INTEGRIN genetics , *CYTOPLASM , *BLOOD platelet aggregation , *POLYMERASE chain reaction - Abstract
Background Kindlins (FERMT) are cytoplasmic proteins required for integrin (ITG) activation, leukocyte transmigration, platelet aggregation and thrombosis. Characterization of kindlins and their association with atherosclerotic plaques in human(s) is lacking. Methods and results Exploratory microarray (MA) was first performed followed by selective quantitative validation of robustly expressed genes with qRT-PCR low-density array (LDA). In LDA, ITGA1 (1.30-fold, p = 0.041) and ITGB3 (1.37-fold, p = 0.036) were upregulated in whole blood samples of patients with coronary artery disease (CAD) compared to healthy controls. In arterial plaques, both robustly expressed transcript variants of FERMT3 (MA: 5.90- and 3.4-fold; LDA: 3.99-fold, p < 0.0001 for all) and ITGB2 (MA: 4.81- and 4.92-fold; LDA: 5.29-fold, p < 0.0001 for all) were upregulated while FERMT2 was downregulated (MA: −1.61-fold; LDA: −2.88-fold, p < 0.0001 for both). The other integrins (ITGA1, ITGAV, ITGB3, ITGB5) were downregulated. All these results were replicated in at least one arterial bed. The latter FERMT3 transcript variant associated with unstable plaques (p = 0.0004). FERMT3 correlated with M2 macrophage markers and in hierarchical cluster analysis clustered with inflammatory and macrophage markers, while FERMT2 correlated with SMC-rich plaque markers and clustered with SMC markers. In confocal immunofluorescence analysis, FERMT3 protein colocalized with abundant CD68-positive cells of monocytic origin in the atherosclerotic plaques, while co-localization of FERMT3 with HHF35 indicative of smooth muscle cells was low. Conclusions Kindlin-3 (FERMT3) is upregulated in atherosclerotic, especially unstable plaques, mainly in cells of monocytic origin and of M2 type. Simultaneous upregulation of ITGB2 suggests a synergistic effect on leukocyte adherence and transmigration into the vessel wall. [ABSTRACT FROM AUTHOR]
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- 2015
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5. A comparison of the accuracy of Illumina HumanHT-12 v3 Expression BeadChip and TaqMan qRT-PCR gene expression results in patient samples from the Tampere Vascular Study
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Raitoharju, Emma, Seppälä, Ilkka, Lyytikäinen, Leo-Pekka, Levula, Mari, Oksala, Niku, Klopp, Norman, Illig, Thomas, Laaksonen, Reijo, Kähönen, Mika, and Lehtimäki, Terho
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ATHEROSCLEROTIC plaque , *GENE expression , *REVERSE transcriptase polymerase chain reaction , *COMPARATIVE studies , *STATISTICAL correlation , *MEDICAL statistics - Abstract
Abstract: Aims: This study was set up to compare the accuracy, sensitivity and specificity of gene expression results between the Illumina HumanHT-12 v3 Expression BeadChip (GWE) and the TaqMan qRT-PCR low-density array (LDA) in atherosclerotic plaques. Methods: Gene expression levels of 196 genes were determined from 22 atherosclerotic samples and 6 controls with both the GWE and the LDA. Results: The accuracies of GWE in comparison to that of qRT-PCR for absolute fold changes (FC) 1.2, 1.6, 2.0 and 3.0 between cases and controls were 73.5%, 79.1%, 72.4% and 60.7%, respectively. The correlation of expression measurements between these methods was good (r = 0.87, y = 0.151 + 0.586x), and the Bland–Altman plot showed that for highly up- or down-regulated transcripts, GWE yields lower absolute FC values than LDA. Conclusion: Gene expression results obtained with the GWE are replicated with high accuracy in LDA, even for technically demanding atherosclerotic samples. [Copyright &y& Elsevier]
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- 2013
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6. Proprotein convertases in human atherosclerotic plaques: The overexpression of FURIN and its substrate cytokines BAFF and APRIL
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Turpeinen, Hannu, Raitoharju, Emma, Oksanen, Anna, Oksala, Niku, Levula, Mari, Lyytikäinen, Leo-Pekka, Järvinen, Otso, Creemers, John W.M., Kähönen, Mika, Laaksonen, Reijo, Pelto-Huikko, Markku, Lehtimäki, Terho, and Pesu, Marko
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ATHEROSCLEROTIC plaque , *ENZYMES , *GENE expression , *CYTOKINES , *CHOLESTEROL metabolism , *ATHEROSCLEROSIS , *IMMUNOHISTOCHEMISTRY - Abstract
Abstract: Background: Proprotein convertase subtilisin/kexin (PCSK) enzymes cleave proproteins into mature end products. Previously, MBTPS1 and PCSK9 have been shown to regulate cholesterol metabolism and LDL receptor recycling, whereas FURIN and PCSK5 have been suggested to inactivate lipases and regulate inflammation in atherosclerosis. Here, we systematically analyzed the expression of PCSKs and their targets in advanced atherosclerotic plaques. Methods and results: Microarray and quantitative real-time PCR experiments showed that FURIN (42.86 median fold, p =2.1e−8), but no other PCSK, is universally overexpressed in the plaques of different vascular regions. The mRNA expression screen of PCSK target proteins in plaques identified many known factors, but it also identified the significant upregulation of the previously overlooked furin-processed B cell activating cytokines APRIL (TNFSF13, 2.52 median fold, p =3.0e−5) and BAFF (TNFSF13B, 2.97 median fold, p =7.6e−6). The dysregulation of FURIN did not associate with its htSNPs or the previously reported regulatory SNP (−229, rs4932178) in the promoter. Immunohistochemistry experiments showed the upregulation of FURIN in the plaque lymphocytes and macrophages where it was co-expressed with BAFF/TNFSF13B and APRIL/TNFSF13. Conclusions: Our data unequivocally show that FURIN is the primary PCSK that is dysregulated in the immune cells of advanced human atherosclerotic plaques, which implies a role for this enzyme in plaque pathology. Therefore, drugs that inhibit FURIN in arteries may modulate the course of this disease. [Copyright &y& Elsevier]
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- 2011
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