14 results on '"Levula, Mari"'
Search Results
2. Interleukin 18 gene promoter polymorphism: a link between hypertension and pre-hospital sudden cardiac death: the Helsinki Sudden Death Study
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Hernesniemi, Jussi A., Karhunen, Pekka J., Oksala, Niku, Kähönen, Mika, Levula, Mari, Rontu, Riikka, Ilveskoski, Erkki, Kajander, Olli, Goebeler, Sirkka, Viiri, Leena E., Hurme, Mikko, and Lehtimäki, Terho
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- 2009
3. Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death
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Kytömäki Leena, Salenius Juha-Pekka, Vihinen Mauno, Thusberg Janita, Oksala Niku, Järvinen Otso, Kajander Olli A, Ilveskoski Erkki, Mikkelsson Jussi, Karhunen Pekka J, Levula Mari, Fan Yue-Mei, Soini Juhani T, Laaksonen Reijo, and Lehtimäki Terho
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Background Disturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2) and the SREBF cleavage-activating protein (SCAP). We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314) and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD). Methods Whole genome expression profiling was completed in twenty vascular samples from carotid, aortic and femoral atherosclerotic plaques and six control samples from internal mammary arteries. Three hundred sudden pre-hospital deaths of middle-aged (33–69 years) Caucasian Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death Study. Coronary narrowing and areas of coronary wall covered with fatty streaks or fibrotic, calcified or complicated lesions were measured and related to the SREBF-2 and SCAP genotypes. Results Whole genome expression profiling showed a significant (p = 0.02) down-regulation of SREBF-2 in atherosclerotic carotid plaques (types IV-V), but not in the aorta or femoral arteries (p = NS for both), as compared with the histologically confirmed non-atherosclerotic tissues. In logistic regression analysis, a significant interaction between the SREBF-2 1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p = 0.046). Men with the SREBF-2 C allele and the SCAP G allele had a significantly increased risk of SCD (OR 2.68, 95% CI 1.07–6.71), compared to SCAP AA homologous subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having complicated lesions and for the occurrence of thrombosis were found, although the results were not statistically significant. Conclusion The results suggest that the allelic variants (SREBF-2 1784G>C and SCAP 2386A>G) in the cholesterol homeostasis regulating SREBF-SCAP pathway may contribute to SCD in early middle-aged men.
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- 2008
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4. Gene expression profiles in Finnish twins with multiple sclerosis
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Kaprio Jaakko, Lehtimäki Terho, Airla Nina, Levula Mari, Paalavuo Raija, Kuusisto Hanna, Särkijärvi Silja, Koskenvuo Markku, and Elovaara Irina
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Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Since genetic alterations influencing susceptibility to multiple sclerosis (MS), the most common autoimmune demyelinating disease of the central nervous system (CNS), are as yet poorly understood, the purpose of this study was to identify genes responsible for MS by studying monozygotic (MZ) twin pairs discordant for MS. Methods In order to identify genes involved in MS development, the gene expression profiles in blood mononuclear cells obtained from eight MZ twin pairs discordant for MS were analyzed by cDNA microarray technology detecting the expression of 8 300 genes. The twins were collected from the Finnish Twin Cohort Study and both affected subjects and their healthy siblings underwent neurological evaluation and cerebral and spinal magnetic resonance imaging. Gene expressions were confirmed by relative quantitative reverse transcription PCR. Results It appeared that 25 genes were at least two-fold up-regulated and 15 genes down-regulated in 25% (2/8) of twins with MS when compared to their healthy siblings. Moreover, 6/25 genes were up-regulated in 40% of MS twins and one gene, interferon alpha-inducible protein (clone IFI-6-16) (G1P3), in 50% of them. The six most constantly expressed genes are (1) G1P3, (2) POU domain, class 3, transcription factor 1, (3) myxovirus resistance 2, (4) lysosomal-associated multispanning membrane protein-5, (5) hemoglobin alpha 2 and (6) hemoglobin beta. Conclusion Over two-fold up-regulation of these six genes in almost half of MZ twins with MS suggests their role in MS pathogenesis. Studies using MZ MS twins obtained from genetically homogeneous population offer a unique opportunity to explore the genetic nature of MS.
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- 2006
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5. Differentially expressed genes and canonical pathways in the ascending thoracic aortic aneurysm – The Tampere Vascular Study
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Sulkava, Miska, primary, Raitoharju, Emma, additional, Mennander, Ari, additional, Levula, Mari, additional, Seppälä, Ilkka, additional, Lyytikäinen, Leo-Pekka, additional, Järvinen, Otso, additional, Illig, Thomas, additional, Klopp, Norman, additional, Mononen, Nina, additional, Laaksonen, Reijo, additional, Kähönen, Mika, additional, Oksala, Niku, additional, and Lehtimäki, Terho, additional
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- 2017
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6. Differentially expressed genes and canonical pathway expression in human atherosclerotic plaques – Tampere Vascular Study
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Sulkava, Miska, primary, Raitoharju, Emma, additional, Levula, Mari, additional, Seppälä, Ilkka, additional, Lyytikäinen, Leo-Pekka, additional, Mennander, Ari, additional, Järvinen, Otso, additional, Zeitlin, Rainer, additional, Salenius, Juha-Pekka, additional, Illig, Thomas, additional, Klopp, Norman, additional, Mononen, Nina, additional, Laaksonen, Reijo, additional, Kähönen, Mika, additional, Oksala, Niku, additional, and Lehtimäki, Terho, additional
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- 2017
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7. Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque
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Fan, Yue-Mei, Hernesniemi, Jussi, Oksala, Niku, Levula, Mari, Raitoharju, Emma, Collings, Auni, Lyytikäinen, Leo-Pekka, Seppälä, Ilkka, Salenius, Juha-Pekka, Laaksonen, Reijo, Kähönen, Mika, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lääketieteen yksikkö - School of Medicine, and University of Tampere
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Biolääketieteet - Biomedicine - Abstract
Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged 31.9 ± 4.9) with lipids and cIMT data were included. For functional study, whole genome mRNA expression profiling was performed in 91 histologically classified atherosclerotic samples. In females, serum total, LDL cholesterol and apoB levels increased gradually according to USF1 rs2516839 genotypes TT < CT < CC and rs1556259 AA < AG < GG as well as according to USF1 H3 (GCCCGG) copy number 0 < 1 < 2. Furthermore, the carriers of minor alleles of rs2516839 (C) and rs1556259 (G) of USF1 gene had decreased USF1 expression in atherosclerotic plaques (P = 0.028 and 0.08, respectively) as compared to non-carriers. The genetic variation in USF1 influence USF1 transcript expression in advanced atherosclerosis and regulates levels and metabolism of circulating apoB and apoB-containing lipoprotein particles in sex-dependent manner, but is not a major determinant of early markers of atherosclerosis.
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- 2014
8. Genes involved in systemic and arterial bed dependent atherosclerosis - Tampere Vascular Study
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Levula, Mari, Oksala, Niku, Airla, Nina, Laaksonen, Reijo, Kähönen, Mika, Pelto-Huikko, Markku, Lehtimäki, Terho, Lääketieteen yksikkö - School of Medicine, and University of Tampere
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Biolääketieteet - Biomedicine - Abstract
Background Atherosclerosis is a complex disease with hundreds of genes influencing its progression. In addition, the phenotype of the disease varies significantly depending on the arterial bed. Methodology/Principal Findings We characterized the genes generally involved in human advanced atherosclerotic (AHA type V–VI) plaques in carotid and femoral arteries as well as aortas from 24 subjects of Tampere Vascular study and compared the results to non-atherosclerotic internal thoracic arteries (n=6) using genome-wide expression array and QRT-PCR. In addition we determined genes that were typical for each arterial plaque studied. To gain a comprehensive insight into the pathologic processes in the plaques we also analyzed pathways and gene sets dysregulated in this disease using gene set enrichment analysis (GSEA). According to the selection criteria used (>3.0 fold change and p-value
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- 2012
9. Gene expression profiling of human lipoprotein-loaded macrophages and atherosclerotic lesions with special emphasis on ADAMs
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Levula, Mari, Lääketieteen laitos - Medical School, Lääketieteellinen tiedekunta - Faculty of Medicine, and University of Tampere
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geeni ,ateroskleroosi ,tulehdus ,inflammation ,Kliininen kemia - Clinical Chemistry ,gene expression ,mikroarray ,atherosclerosis ,microarray ,LDL - Abstract
Ateroskleroosi on monitekijäinen sairaus, jonka kehittymiseen vaikuttavat perimä ja ympäristötekijät. Sairaus aiheuttaa vuosikymmenien saatossa valtimoiden tukkeutumista, mikä johtaa verenkiertohäiriöihin sydämessä, aivoissa ja alaraajoissa. Koska plasman korkea LDL- (low-density lipoprotein) kolesterolipitoisuus on ateroskleroosin huomattavimpia riskitekijöitä, on ateroskleroosin uskottu johtuvan pääasiallisesti rasva-aineiden kerääntymisestä verisuonen seinämään. Nykykäsityksen mukaan ateroskleroosia voidaan kuitenkin tarkastella kroonisena tulehdussairautena, jonka etenemisessä etenkin hapettuneilla lipoproteiineilla, monosyyteistä erilaistuneilla makrofageilla ja T-soluilla on merkittävä rooli. Ateroskleroosin syntymiseen ja etenemiseen vaikuttavia tekijöitä voidaan tutkia selvittämällä sairaudessa ilmentyviä geenejä tai usean geenin muodostamia aineenvaihduntateitä. Tässä väitöskirjatyössä pyrittiin löytämään geenejä, jotka vaikuttavat ateroskleroosin syntymiseen ja kehittymiseen. Tutkimuksessa pyrittiin selvittämään ateroskleroosin alkuvaiheen verisuonimuutoksiin liittyviä geenejä tutkimalla ihmisen monosyytti-makrofagien geenien ilmentymisen muuttumista altistettaessa niitä normaaleille ja hapettuneille LDL- ja HDL- (high-density lipoprotein) hiukkasille. Tutkimuksessa havaittiin hapettuneiden LDL- ja HDL-hiukkasten vaikutuksen olevan pääasiallisesti vastakkainen monosyytti-makrofagien geenien ilmentymiseen, vaikkakin huomattava osa geeneistä ilmentyi samansuuntaisesti lipoproteiinikäsittelyiden jälkeen. Elimistössä myös HDL-hiukkaset ovat alttiita hapettumiselle, joten tutkimuksen perusteella myös hapettuneet HDL-hiukkaset voivat myötävaikuttaa ateroskleroosin kehittymiseen. Tutkimuksessa havaittiin useita uusia ateroskleroosin varhaisvaiheisiin mahdollisesti liittyviä geenejä, joita ei oltu aikaisemmin liitetty ateroskleroosiin. Soluviljelykokeiden lisäksi tutkimuksessa kartoitettiin ihmisten kaikkien geenien ilmentyminen ateroskleroottisissa kaula-, reisi- ja aortta-valtimoissa sekä terveissä rintakehän seinämävaltimoissa ja pyrittiin löytämään geenejä, jotka osallistuvat pidemmälle edenneen ateroskleroottisen vaurion kehittymiseen. Tutkimuksessa selvitettiin ateroskleroottisissa valtimoissa eniten ja vähiten ilmentyvät yksittäiset geenit, sairaudessa muuntuneet geenien toiminnalliset kokonaisuudet ja aineenvaihduntatiet, sekä karakterisoitiin kullekin ateroskleroottisille valtimoille ominaiset geenien ilmentymisen muutokset. Koko perimän laajuisia geenien ilmentymisen tutkimuksia on tehty aikaisemminkin, mutta tässä tutkimuksessa selvitettiin ensimmäistä kertaa kolmessa ateroskleroottisessa valtimossa ilmentyvät geenit sekä kuvattiin yksittäisiä geenejä, jotka ovat aktiivisena ainoastaan tietyn valtimon ateroskleroosissa. Koska ateroskleroosi on sairaus, johon osallistuu kymmeniä, ellei satoja geenejä, auttavat tutkimuksessa selvitetyt ateroskleoottisissa valtimoissa muuntuneet aineenvaihduntatiet ymmärtämään kokonaisvaltaisesti ateroskleroosin kehittymistä. Tutkimuksessa havaittiin myös yksittäisiä geenejä, joiden ilmentymisen havaittiin muuttuneen ainoastaan ateroskleroottisessa aortta- tai reisivaltimossa. Tälläisten kullekin ateroskleroottiselle valtimolle ominaisten geenien selvittäminen auttaa ymmärtämään näihin valtimoihin kehittyvän sairauden erityispiirteitä. Tutkittaessa kaikkien ihmisten geenien ilmentymistä ateroskleroottisissa valtimoissa, havaittiin ADAM- (A Disintegrin And Metalloprotease) metalloproteaasien ilmentymisen muuttuneen sairaissa valtimoissa verrattuna terveisiin valtimoihin. Tutkimuksessa havaittiin ADAM8, -9, -15 ja -17 mRNA:n ja proteiinien määrän lisääntyneen ateroskleroottisissa vaurioissa ja ADAM8 geenivariaation liittyvän komplisoituneiden ateroskleroottisten vaurioiden pinta-alaan ja sydänäkkikuolemaan. ADAM-metalloproteaasien yhteyttä ateroskleroosin on tutkittu maailmalla vähän ja tulos ADAM8:n yhteydestä ateroskleroosin on uusi. Koska ADAM-metalloproteaaseilla on useita ateroskleroosin kannalta mielenkiintoisia ominaisuuksia, esimerkiksi sytokiinien ja kasvutekijöiden aktivointi tai inaktivointi, voi lisääntynyt ADAM-metalloproteaasien ilmentyminen ateroskleroosissa vaikuttaa huomattavasti sairaudelle tyypillisen tulehdusprosessin etenemiseen. Atherosclerosis is the most important cause of cardiovascular diseases and globally, the major cause of death. Generally, atherosclerosis can be considered to be a form of chronic inflammation resulting from interaction between modified lipoproteins, monocyte-derived macrophages, T cells, and the normal cellular elements of the arterial wall. The objectives of the thesis were to 1) study the gene expression changes induced by oxidized low-density lipoprotein (ox-LDL) and oxidized high-density lipoprotein (ox-HDL) molecules in cultured human monocyte-macrophages, 2) study the gene expression changes that prevail in advanced human atherosclerotic arteries, 3) define the expression of ADAM8 mRNA and protein in atherosclerotic arteries and study if there is an association of its 2662 T/G allelic variant (rs2995300) with atherosclerosis and myocardial infarction (MI) and 4) define the expression of ADAM9, -15 and -17 mRNA and protein in human atherosclerotic plaques and identify their catalytically active forms in the plaques. The gene expression changes characterizing early atherosclerotic lesion formation were studied with cDNA microarray and quantitative RT-PCR (QRT-PCR) using cultured human monocyte-macrophages obtained from leukocyte-rich buffy coats collected from healthy blood donors. The Tampere Vascular Study (TVS) material was used to evaluate the gene expression changes prevailing in advanced human atherosclerotic arteries using genome-wide oligonucleotide array. The TVS study material consisted altogether of 24 atherosclerotic arteries and six non atherosclerotic control arteries. Atherosclerotic arteries were collected from carotid and femoral arteries as well as abdominal aortas. Internal thoracic arteries were used as controls. Gene expression changes were verified with QRT-PCR and the localization of the ADAM proteins studied was studied with immunohistochemistry. The association of ADAM8 allelic variant with atherosclerosis and MI was analyzed with TaqMan 5´exonuclease assay and fluorescent allele-specific TagMan probes using the Helsinki Sudden Death Study (HSDS) material. 1) Ox-LDL and ox-HDL significantly affected the gene expression profiles of monocyte-macrophages. Lipoprotein treatments (LDL vs. HDL) mainly induced opposite expression in the gene expression of monocyte-macrophages but in addition, a significant number of genes was found to respond similarly to lipoprotein treatments. Several new candidate genes for foam cell formation were found. 2) Using genome-wide gene expression array (GWEA), we characterized the generally most up- and down-regulated genes in atherosclerotic plaques and found eight genes specific for aortic plaques and three genes for femoral plaques. In addition, a total of 28 pathways dysregulated (20 up- and 8 down-regulated compared to non-atherosclerotic controls) in plaques were defined with special emphasis on a T cell chemokine pathway. 3-4) The expression of ADAM8, -9, -15 and -17 were found to be significantly induced in the atherosclerotic plaques and the allelic variant of ADAM8 (rs2995300) was significantly associated with the area of complicated atherosclerotic plaques and fatal MI in HSDS material. Microarray technology was found to be applicable in the screening of gene expression changes in lipoprotein-loaded monocyte-macrophages as well as in advanced human atherosclerotic arteries. Several novel candidate genes and pathways potentially involved in the development of atherosclerosis were found. The pronounced expression of ADAM8, -9, -15, and -17 in the atherosclerotic plaque and the association of ADAM8 allelic variant with the areas of complicated atherosclerotic plaques and fatal myocardial infarct support the involvement of ADAMs in atherosclerosis.
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- 2009
10. Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque
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Fan, Yue-Mei, primary, Hernesniemi, Jussi, additional, Oksala, Niku, additional, Levula, Mari, additional, Raitoharju, Emma, additional, Collings, Auni, additional, Hutri-Kähönen, Nina, additional, Juonala, Markus, additional, Marniemi, Jukka, additional, Lyytikäinen, Leo-Pekka, additional, Seppälä, Ilkka, additional, Mennander, Ari, additional, Tarkka, Matti, additional, Kangas, Antti J., additional, Soininen, Pasi, additional, Salenius, Juha Pekka, additional, Klopp, Norman, additional, Illig, Thomas, additional, Laitinen, Tomi, additional, Ala-Korpela, Mika, additional, Laaksonen, Reijo, additional, Viikari, Jorma, additional, Kähönen, Mika, additional, Raitakari, Olli T., additional, and Lehtimäki, Terho, additional
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- 2014
- Full Text
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11. Genes Involved in Systemic and Arterial Bed Dependent Atherosclerosis - Tampere Vascular Study
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Levula, Mari, primary, Oksala, Niku, additional, Airla, Nina, additional, Zeitlin, Rainer, additional, Salenius, Juha-Pekka, additional, Järvinen, Otso, additional, Venermo, Maarit, additional, Partio, Teemu, additional, Saarinen, Jukka, additional, Somppi, Taija, additional, Suominen, VeliPekka, additional, Virkkunen, Jyrki, additional, Hautalahti, Juha, additional, Laaksonen, Reijo, additional, Kähönen, Mika, additional, Mennander, Ari, additional, Kytömäki, Leena, additional, Soini, Juhani T., additional, Parkkinen, Jyrki, additional, Pelto-Huikko, Markku, additional, and Lehtimäki, Terho, additional
- Published
- 2012
- Full Text
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12. Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death
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Fan, Yue-Mei, primary, Karhunen, Pekka J, additional, Levula, Mari, additional, Ilveskoski, Erkki, additional, Mikkelsson, Jussi, additional, Kajander, Olli A, additional, Järvinen, Otso, additional, Oksala, Niku, additional, Thusberg, Janita, additional, Vihinen, Mauno, additional, Salenius, Juha-Pekka, additional, Kytömäki, Leena, additional, Soini, Juhani T, additional, Laaksonen, Reijo, additional, and Lehtimäki, Terho, additional
- Published
- 2008
- Full Text
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13. Gene expression profiles in Finnish twins with multiple sclerosis
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Särkijärvi, Silja, primary, Kuusisto, Hanna, additional, Paalavuo, Raija, additional, Levula, Mari, additional, Airla, Nina, additional, Lehtimäki, Terho, additional, Kaprio, Jaakko, additional, Koskenvuo, Markku, additional, and Elovaara, Irina, additional
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- 2006
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14. Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque.
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Yue-Mei Fan, Hernesniemi, Jussi, Oksala, Niku, Levula, Mari, Raitoharju, Emma, Collings, Auni, Hutri-Kähönen, Nina, Juonala, Markus, Marniemi, Jukka, Lyytikäinen, Leo-Pekka, Seppälä, Ilkka, Mennander, Ari, Tarkka, Matti, Kangas, Antti J., Soininen, Pasi, Salenius, Juha Pekka, Klopp, Norman, Illig, Thomas, Laitinen, Tomi, and Ala-Korpela, Mika
- Subjects
TRANSCRIPTION factors ,LIPOPROTEINS ,METABOLISM ,ATHEROSCLEROTIC plaque ,ATHEROSCLEROSIS ,LIPIDS ,MESSENGER RNA - Abstract
Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged 31.9 ± 4.9) with lipids and cIMT data were included. For functional study, whole genome mRNA expression profiling was performed in 91 histologically classified atherosclerotic samples. In females, serum total, LDL cholesterol and apoB levels increased gradually according to USF1 rs2516839 genotypes TT
- Published
- 2014
- Full Text
- View/download PDF
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