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Activated immune-inflammatory pathways are associated with long-standing depressive symptoms: Evidence from gene-set enrichment analyses in the Young Finns Study.

https://arctichealth.org/en/permalink/ahliterature275217
Source
J Psychiatr Res. 2015 Dec;71:120-5
Publication Type
Article
Date
Dec-2015
Author
Marko Elovainio
Tuukka Taipale
Ilkka Seppälä
Nina Mononen
Emma Raitoharju
Markus Jokela
Laura Pulkki-Råback
Thomas Illig
Melanie Waldenberger
Christian Hakulinen
Taina Hintsa
Mika Kivimäki
Mika Kähönen
Liisa Keltikangas-Järvinen
Olli Raitakari
Terho Lehtimäki
Source
J Psychiatr Res. 2015 Dec;71:120-5
Date
Dec-2015
Language
English
Publication Type
Article
Keywords
Adult
Depressive Disorder - epidemiology - immunology
Female
Finland - epidemiology
Gene Expression Profiling
Humans
Male
Prospective Studies
Psychiatric Status Rating Scales
Severity of Illness Index
Abstract
We used genome wide expression (GWE) data of circulating blood cells and pathway analysis to investigate the inflammatory and other molecular pathways that may be associated with long-standing depressive symptoms. Participants were 607 women and 316 men (mean age 42 years) from the Young Finns Study who participated in three consecutive study phases in 2001, 2007 and 2012. Using Gene-set enrichment analyses (GSEA) we focused our analyses to pathways (available in MSigDB database) that are likely to affect immunological and inflammatory processes. GSEA were performed for blood cell GWE data in 2012. Depressive symptoms were assessed using a modified 21-item Beck Depression Inventory in each of the three study phases. Participants who scored in the top quartile of depressive symptoms in each of the three measurement points (n = 191) differed from other participants (n = 732) in several gene-set pathways related to inflammatory processes or immune-inflammatory signaling including interleukin (IL-1) pathway, and pathways related to various immuno-inflammatory processes, such as toll-like, the NEF protein, the nuclear factor kB, the kinase AKT and the mature B cell antigen receptor pathway (false discovery rates, FDRs
PubMed ID
26473696 View in PubMed
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Activation of indoleamine 2,3-dioxygenase-induced tryptophan degradation in advanced atherosclerotic plaques: Tampere vascular study.

https://arctichealth.org/en/permalink/ahliterature147142
Source
Ann Med. 2010;42(1):55-63
Publication Type
Article
Date
2010
Author
Petri Niinisalo
Niku Oksala
Mari Levula
Markku Pelto-Huikko
Otso Järvinen
Juha-Pekka Salenius
Leena Kytömäki
Juhani T Soini
Mika Kähönen
Reijo Laaksonen
Mikko Hurme
Terho Lehtimäki
Author Affiliation
Department of Clinical Chemistry, University of Tampere, Medical School, and Tampere University Hospital, Centre for Laboratory Medicine, Tampere, Finland. petri.niinisalo@uta.fi
Source
Ann Med. 2010;42(1):55-63
Date
2010
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Antigen-Presenting Cells - metabolism - pathology
Antigens, CD - chemistry - metabolism
Antigens, CD28 - metabolism
Antigens, Differentiation, Myelomonocytic - chemistry
Antigens, Differentiation, T-Lymphocyte - metabolism
Atherosclerosis - enzymology - immunology - pathology
CTLA-4 Antigen
Female
Finland
Forkhead Transcription Factors - metabolism
Gene Expression
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism
Inducible T-Cell Co-Stimulator Protein
Macrophages - immunology
Male
Middle Aged
Monocytes - immunology
T-Lymphocytes, Regulatory - immunology
Tryptophan - metabolism
Abstract
We aimed to characterize the expression of indoleamine 2,3-dioxygenase (IDO) or IDO-induced tryptophan degradation-dependent pathways, which may lead to suppression of T cells and possible protection against atherosclerosis.
Expression of IDO and IDO-related pathway components was analyzed in advanced human atherosclerotic plaques (n = 24) and in non-atherosclerotic arteries (n = 6). Up-regulation of IDO and genes related to the IDO pathway was found to be pronounced in atherosclerotic plaques. Immunohistochemistry demonstrated IDO protein in the atheromatous core and co-distribution with monocyte-macrophages (CD68-positive cells). In gene-set enrichment analysis, the IDO pathway revealed a significant (false discovery rate (FDR) = 0.07) regulatory T cell, fork-head box protein 3 (FoxP3)-initiated CD28-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-inducible T cell co-stimulator (ICOS)-driven pathway leading to activation of IDO expression in antigen-presenting cells (APCs). Expression of these IDO pathway genes varied between 2.1- and 16.8-fold as compared to control tissues (P
PubMed ID
19941414 View in PubMed
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ADAM8 and its single nucleotide polymorphism 2662 T/G are associated with advanced atherosclerosis and fatal myocardial infarction: Tampere vascular study.

https://arctichealth.org/en/permalink/ahliterature149907
Source
Ann Med. 2009;41(7):497-507
Publication Type
Article
Date
2009
Author
Mari Levula
Nina Airla
Niku Oksala
Jussi A Hernesniemi
Markku Pelto-Huikko
Juha-Pekka Salenius
Rainer Zeitlin
Otso Järvinen
Ari-Pekka J Huovila
Seppo T Nikkari
Olli Jaakkola
Erkki Ilveskoski
Jussi Mikkelsson
Markus Perola
Reijo Laaksonen
Leena Kytömäki
Juhani T Soini
Mika Kähönen
Jyrki Parkkinen
Pekka J Karhunen
Terho Lehtimäki
Author Affiliation
Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, Medical School, University of Tampere, Finland. mari.levula@uta.fi
Source
Ann Med. 2009;41(7):497-507
Date
2009
Language
English
Publication Type
Article
Keywords
ADAM Proteins - genetics - metabolism
Adult
Alleles
Atherosclerosis - epidemiology - genetics - metabolism
Coronary Vessels - pathology
Finland - epidemiology
Gene Expression
Health Surveys - statistics & numerical data
Humans
Immunohistochemistry
Male
Membrane Proteins - genetics - metabolism
Middle Aged
Myocardial Infarction - genetics - mortality
Phenotype
Polymorphism, Single Nucleotide
RNA, Messenger - metabolism
Risk factors
Statistics, nonparametric
Up-Regulation - genetics
Abstract
Previously, we scanned all 23,000 human genes for differential expression between normal and atherosclerotic tissues and found the involvement of ADAM8.
We investigated the expression of ADAM8 mRNA and protein level in human atherosclerotic tissues and non-atherosclerotic internal thoracic arteries as well as the association of ADAM8 2662 T/G single nucleotide polymorphism (SNP) with the extent of coronary atherosclerosis and with the risk of fatal myocardial infarction.
ADAM8 mRNA was up-regulated in carotid, aortic, and femoral atherosclerotic plaques (n=24) when compared with non-atherosclerotic arteries. ADAM8 protein expression was increased in advanced atherosclerotic plaques as compared to control vessels wherein it was localized to macrophages and smooth muscle cells The G allele carriers of the ADAM8 2662 T/G SNP had significantly larger areas of fibrotic, calcified, and complicated plaques in coronary arteries (P=0.027, P=0.011, and P=0.011, respectively) and significantly higher occurrence of myocardial infarction (MI) (P=0.004) and fatal pre-hospital MI (P=0.003) than did the TT homozygotes.
ADAM8 is a promising candidate to be involved in atherosclerosis, and its 2662 T/G allelic variant significantly associates with advanced atherosclerotic lesion areas and MI.
PubMed ID
19575316 View in PubMed
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Adiponectin is related with carotid artery intima-media thickness and brachial flow-mediated dilatation in young adults--the Cardiovascular Risk in Young Finns Study.

https://arctichealth.org/en/permalink/ahliterature140840
Source
Ann Med. 2010 Dec;42(8):603-11
Publication Type
Article
Date
Dec-2010
Author
Liisa A Saarikoski
Risto K Huupponen
Jorma S A Viikari
Jukka Marniemi
Markus Juonala
Mika Kähönen
Olli T Raitakari
Author Affiliation
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Source
Ann Med. 2010 Dec;42(8):603-11
Date
Dec-2010
Language
English
Publication Type
Article
Keywords
Adiponectin - blood
Adult
Atherosclerosis - epidemiology - pathology - physiopathology
Biological Markers - blood
Brachial Artery - physiopathology - ultrasonography
Carotid Arteries - pathology - physiopathology - ultrasonography
Elasticity Imaging Techniques
Female
Finland - epidemiology
Follow-Up Studies
Humans
Male
Regional Blood Flow
Regression Analysis
Risk factors
Tunica Intima - pathology - ultrasonography
Young Adult
Abstract
Adiponectin may be involved in the pathogenesis of atherosclerosis. We investigated the relation of adiponectin on early functional and structural markers of subclinical atherosclerosis in a large population-based cohort of young men and women.
We measured serum adiponectin using radioimmunoassay in 2,147 young adults (ages 24-39 years) participating in the Cardiovascular Risk in Young Finns Study. The subjects had ultrasound data on carotid intima-media thickness (IMT), carotid artery elasticity (n = 2,139) and brachial flow-mediated dilatation (FMD) (n = 1,996). In univariate analysis, adiponectin was inversely associated with IMT (r = -0.16, P
PubMed ID
20839916 View in PubMed
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ADMA concentration changes across the menstrual cycle and during oral contraceptive use: the Cardiovascular Risk in Young Finns Study.

https://arctichealth.org/en/permalink/ahliterature147193
Source
Eur J Endocrinol. 2010 Feb;162(2):259-65
Publication Type
Article
Date
Feb-2010
Author
Pirjo Valtonen
Kari Punnonen
Heli Saarelainen
Nonna Heiskanen
Olli T Raitakari
Markus Juonala
Jorma S A Viikari
Georg Alfthan
Mika Kähönen
Reijo Laaksonen
Tiina Lyyra-Laitinen
Tomi Laitinen
Seppo Heinonen
Author Affiliation
Departments of Clinical Chemistry Obstetrics and Gynaecology, Kuopio University Hospital and University of Kuopio, FIN-70210 Kuopio, Finland.
Source
Eur J Endocrinol. 2010 Feb;162(2):259-65
Date
Feb-2010
Language
English
Publication Type
Article
Keywords
Adult
Arginine - analogs & derivatives - blood
Atherosclerosis - epidemiology - metabolism
Brachial Artery - physiology
C-Reactive Protein - metabolism
Contraceptives, Oral - therapeutic use
Creatinine - blood
Estrogens - therapeutic use
Female
Finland - epidemiology
Humans
Menstrual Cycle - metabolism
Progesterone Congeners - therapeutic use
Prospective Studies
Risk factors
Vasodilation - physiology
Young Adult
Abstract
The aim of this study was to evaluate changes in the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) levels during different menstrual cycle phases in young adult women with or without oral contraceptive (OC) use.
The subjects (n=1079) originated from a large population-based, prospective cohort study conducted in Finland. Plasma ADMA, symmetric dimethylarginine (SDMA), L-arginine, C-reactive protein, creatinine, and brachial artery flow-mediated dilatation (FMD) were measured. The use of OCs and menstrual cycle phase were determined from a questionnaire.
In non-OC users, ADMA (P=0.017), L-arginine (P=0.002), and ADMA/SDMA ratio (P
PubMed ID
19934267 View in PubMed
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Adolescence risk factors are predictive of coronary artery calcification at middle age: the cardiovascular risk in young Finns study.

https://arctichealth.org/en/permalink/ahliterature120679
Source
J Am Coll Cardiol. 2012 Oct 9;60(15):1364-70
Publication Type
Article
Date
Oct-9-2012
Author
Olli Hartiala
Costan G Magnussen
Sami Kajander
Juhani Knuuti
Heikki Ukkonen
Antti Saraste
Irina Rinta-Kiikka
Sakari Kainulainen
Mika Kähönen
Nina Hutri-Kähönen
Tomi Laitinen
Terho Lehtimäki
Jorma S A Viikari
Jaakko Hartiala
Markus Juonala
Olli T Raitakari
Author Affiliation
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, and Turku PET Center, Turku University Hospital, Turku, Finland. olli.hartiala@utu.fi
Source
J Am Coll Cardiol. 2012 Oct 9;60(15):1364-70
Date
Oct-9-2012
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Age Factors
Calcinosis - complications - diagnosis - epidemiology
Child
Child, Preschool
Coronary Artery Disease - epidemiology - etiology - pathology
Coronary Vessels - pathology
Cross-Sectional Studies
Female
Finland - epidemiology
Follow-Up Studies
Humans
Incidence
Male
Middle Aged
Prognosis
Retrospective Studies
Risk Assessment - methods
Time Factors
Young Adult
Abstract
The purpose of this study was to examine the roles of adolescence risk factors in predicting coronary artery calcium (CAC).
Elevated coronary heart disease risk factor levels in adolescence may predict subsequent CAC independently of change in risk factor levels from adolescence to adulthood.
CAC was assessed in 589 subjects 40 to 46 years of age from the Cardiovascular Risk in Young Finns Study. Risk factor levels were measured in 1980 (12 to 18 years) and in 2007.
The prevalence of any CAC was 19.2% (27.9% in men and 12.2% in women). Age, levels of systolic blood pressure (BP), total cholesterol, and low-density lipoprotein cholesterol (LDL-C) in adolescence, as well as systolic BP, total cholesterol, diastolic BP, and pack-years of smoking in adulthood were higher among subjects with CAC than those without CAC. Adolescence LDL-C and systolic BP levels predicted CAC in adulthood independently of 27-year changes in these risk factors. The multivariable odds ratios were 1.34 (95% confidence interval: 1.05 to 1.70; p=0.02) and 1.38 (95% confidence interval: 1.08 to 1.77; p=0.01), for 1-SD increase in adolescence LDL-C and systolic BP, respectively. Exposure to both of these risk factors in adolescence (defined as values at or above the age- and sex-specific 75th percentile) substantially increased the risk of CAC (multivariable odds ratio: 3.5 [95% confidence interval: 1.7 to 7.2; p=0.007]) between groups with no versus both risk factors.
Elevated adolescence LDL-C and systolic BP levels are independent predictors of adulthood CAC, indicating that adolescence risk factor levels play an important role in the pathogenesis of coronary heart disease.
Notes
Comment In: J Am Coll Cardiol. 2012 Oct 9;60(15):1371-322981554
PubMed ID
22981553 View in PubMed
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Adult-type hypolactasia is not a predisposing factor for the early functional and structural changes of atherosclerosis: the Cardiovascular Risk in Young Finns Study.

https://arctichealth.org/en/permalink/ahliterature159355
Source
Clin Sci (Lond). 2008 Nov;115(9):265-71
Publication Type
Article
Date
Nov-2008
Author
Terho Lehtimäki
Nina Hutri-Kähönen
Mika Kähönen
Jukka Hemminki
Vera Mikkilä
Marika Laaksonen
Leena Räsänen
Nina Mononen
Markus Juonala
Jukka Marniemi
Jorma Viikari
Olli Raitakari
Author Affiliation
Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Tampere University Hospital and the Medical School at the University of Tampere, 33014 Tampere, Finland. terho.lehtimaki@uta.fi
Source
Clin Sci (Lond). 2008 Nov;115(9):265-71
Date
Nov-2008
Language
English
Publication Type
Article
Keywords
Adult
Atherosclerosis - epidemiology - etiology - genetics - physiopathology
Brachial Artery - physiopathology - ultrasonography
Carotid Arteries - pathology - ultrasonography
Dairy Products - statistics & numerical data
Diet - statistics & numerical data
Epidemiologic Methods
Female
Finland - epidemiology
Genetic Predisposition to Disease
Genotype
Humans
Lactase - deficiency
Lactase-Phlorizin Hydrolase - genetics
Lactose Intolerance - complications - epidemiology - genetics - pathology
Male
Polymorphism, Genetic
Tunica Intima - pathology - ultrasonography
Tunica Media - pathology - ultrasonography
Vasodilation
Abstract
Individuals suffering from ATH (adult-type hypolactasia), defined by the LCT (gene encoding lactase-phlorizin hydrolase) C/C(-13910) genotype (rs4988235), use less milk and dairy products and may have higher plasma HDL (high-density lipoprotein) and lower triacylglycerol (triglyceride) concentrations than their counterparts without ATH. To investigate the effects of ATH status on the early markers of atherosclerosis, we examined its association with CIMT (carotid intima-media thickness), CAC (carotid artery compliance) and brachial artery FMD (flow-mediated dilation) in a young population-based cohort of otherwise healthy individuals. As part of the Cardiovascular Risk in Young Finns Study, we performed CIMT, CAC and FMD analyses, LCT C/T(-13910) genotyping and risk factor determination in 2109 young subjects 24-39 years of age (45% males) at the time of the examination. The consumption of both milk and dairy products was lowest and the consumption of alcohol highest in subjects with the C/C(-13910) genotype (P
PubMed ID
18194137 View in PubMed
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Age and gender biases in secondary prevention of coronary heart disease in a Finnish university hospital setting.

https://arctichealth.org/en/permalink/ahliterature161542
Source
Clin Drug Investig. 2007;27(10):673-81
Publication Type
Article
Date
2007
Author
Sanna-Maria Michou
Mika Kähönen
Terho Lehtimäki
Kjell Nikus
Jari Viik
Kari Niemelä
Janne Kallio
Rami Lehtinen
Tiit Kööbi
Väinö Turjanmaa
Tuomo Nieminen
Author Affiliation
Department of Pharmacological Sciences, Medical School, University of Tampere, Tampere, Finland.
Source
Clin Drug Investig. 2007;27(10):673-81
Date
2007
Language
English
Publication Type
Article
Keywords
Adrenergic beta-Antagonists - therapeutic use
Adult
Age Factors
Aged
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Aspirin - therapeutic use
Cardiovascular Agents - therapeutic use
Cohort Studies
Coronary Disease - prevention & control
Exercise Test
Female
Finland
Hospitals, University
Humans
Hypercholesterolemia - complications
Hypertension - complications
Male
Middle Aged
Physician's Practice Patterns - standards
Risk factors
Sex Factors
Smoking
Abstract
Several studies have shown that treatment of coronary heart disease (CHD) does not meet the goals set in recommendations. The aim of this study was to investigate the adequacy of CHD drug treatment and secondary prevention measures, particularly with respect to age and gender biases, in a Finnish university hospital setting.
The participant pool consisted of patients in FINCAVAS (Finnish Cardiovascular Study), which is a cohort study recruiting consecutive patients performing a clinical exercise test at Tampere University Hospital, Tampere, Finland. 802 patients (581 men, 221 women) with a prior diagnosis of CHD recruited between October 2001 and December 2004 were included in the analysis.
Only roughly 12% of both men and women had an optimal risk factor profile. High blood pressure and hypercholesterolaemia were more common in women than in men, whereas smoking was more frequent among men. Men used ACE inhibitors (32.9% vs 20.4%, respectively), beta-adrenoceptor antagonists (80.8% vs 68.3%, respectively) and aspirin (acetylsalicylic acid) [69.7% vs 58.8%, respectively] more frequently than women, but the frequency of use of these medications was also not at the recommended levels in men. Risk factor control is poorer in older than younger age groups.
CHD patients, particularly women, who performed an exercise stress test in a university hospital are suboptimally treated.
PubMed ID
17803342 View in PubMed
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Alcohol consumption is directly associated with carotid intima-media thickness in Finnish young adults: the Cardiovascular Risk in Young Finns Study.

https://arctichealth.org/en/permalink/ahliterature153337
Source
Atherosclerosis. 2009 Jun;204(2):e93-8
Publication Type
Article
Date
Jun-2009
Author
Markus Juonala
Jorma S A Viikari
Mika Kähönen
Tomi Laitinen
Leena Taittonen
Britt-Marie Loo
Antti Jula
Jukka Marniemi
Leena Räsänen
Tapani Rönnemaa
Olli T Raitakari
Author Affiliation
University of Turku, Department of Medicine, Finland. markus.juonala@utu.fi
Source
Atherosclerosis. 2009 Jun;204(2):e93-8
Date
Jun-2009
Language
English
Publication Type
Article
Keywords
Adult
Alcohol Drinking - adverse effects - epidemiology
Cardiovascular Diseases - epidemiology - etiology
Carotid Arteries - ultrasonography
Carotid Artery Diseases - epidemiology - etiology - ultrasonography
Cross-Sectional Studies
Female
Finland - epidemiology
Humans
Linear Models
Male
Risk assessment
Risk factors
Tunica Intima - ultrasonography
Tunica Media - ultrasonography
Young Adult
Abstract
There is substantial epidemiological data suggesting a J- or U-shaped association between alcohol consumption and coronary events. However, some studies in experimental animals suggest that alcohol may increase atherosclerosis. Therefore, our aim was to study whether alcohol consumption is associated with carotid intima-media thickness (IMT), marker of subclinical atherosclerosis, in young, healthy adults.
Alcohol consumption, carotid IMT and conventional cardiovascular risk factors were investigated in 2074 subjects, aged 24-39 years.
In subjects consuming none, >0 to or=4 units of alcohol per day, the respective carotid IMT values were 0.57+/-0.004, 0.59+/-0.003, 0.59+/-0.006, and 0.60+/-0.012 mm (mean+/-S.E.M., P
PubMed ID
19124122 View in PubMed
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Aortic sinus diameter in middle age is associated with body size in young adulthood.

https://arctichealth.org/en/permalink/ahliterature297426
Source
Heart. 2018 05; 104(9):773-778
Publication Type
Journal Article
Date
05-2018
Author
Jussi A Hernesniemi
Jarkko Heiskanen
Saku Ruohonen
Noora Kartiosuo
Nina Hutri-Kähönen
Mika Kähönen
Eero Jokinen
Päivi Tossavainen
Merja Kallio
Tomi Laitinen
Terho Lehtimäki
Jorma S A Viikari
Markus Juonala
Olli T Raitakari
Author Affiliation
Department of Cardiology, Tays Heart Hospital, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
Source
Heart. 2018 05; 104(9):773-778
Date
05-2018
Language
English
Publication Type
Journal Article
Keywords
Adolescent
Adult
Body Size - physiology
Body surface area
Child
Child, Preschool
Echocardiography
Female
Finland
Follow-Up Studies
Humans
Longitudinal Studies
Male
Middle Aged
Sinus of Valsalva - anatomy & histology
Young Adult
Abstract
Aortic sinus dilatation can lead to aortic valve regurgitation or even aortic dissection. Our objective was to examine the association between body surface area (BSA) measures from childhood to middle age and aortic sinus diameter in middle age. Understanding the relation of these two clarifies how aortic size is normally determined.
Cardiovascular Risk in Young Finns Study is a longitudinal study with follow-up of over 31 years (1980-2011). The study comprises information of body composition from multiple time points of 1950 subjects with cardiac ultrasound measurements made in 2011. The association between BSA in different ages and aortic sinus diameter in middle age was analysed by linear regression modelling adjusted with age, sex and diastolic blood pressure. Missing BSA values were derived for each life year (ages 3-33 years) from subject-specific curves for body weight and height estimated from longitudinal measurements using mixed model regression splines.
BSA estimates in early 20s are most strongly associated with aortic sinus diameter in middle age. Top association was observed at age 23 years with one SD increase in estimated BSA corresponding to 1.04?mm (0.87-1.21?mm) increase in aortic diameter. Increase in body weight beyond early 20s does not associate with aortic sinus diameter, and the association between middle age BSA and aortic size is substantially weaker (0.74?mm increase (0.58-0.89?mm)). These results were confirmed in a subpopulation using only measured data.
The association between aortic sinus diameter and BSA is stronger when considering BSA in young adulthood compared with BSA in middle age.
PubMed ID
29092920 View in PubMed
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178 records – page 1 of 18.