Browsing by Subject "Atherosclerosis"

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Now showing items 21-32 of 32
  • Ollikainen, Eliisa; Tulamo, Riikka; Lehti, Satu; Hernesniemi, Juha; Niemelä, Mika; Kovanen, Petri T.; Frösen, Juhana (2018)
    Rupture of a saccular intracranial aneurysm (sIA) is often fatal. Thus, early detection of rupture-prone sIAs is vital. Myeloperoxidase (MPO), derived mainly from neutrophils, associates with sIA rupture, and therefore its role in sIA pathogenesis warrants further studies. We analyzed MPO and its association with other histological markers in 36 (16 unruptured and 20 ruptured) sIA samples by immunohistochemistry. MPO was present in all studied sIAs, and its expression associated with wall inflammatory cell infiltrations (r = 0.50, 0.63, and 0.75, all p <0.002), degenerative remodeling (p = 0.002) and rupture (p = 0.003). MPO associated strongly with the presence of organized luminal thrombi (p <0.001), which also stained positive for MPO. Polymorphonuclear MPO+ cells were detected in the sIA walls, indicating neutrophils as MPO-source. MPO correlated strongly with accumulation of oxidized lipids (r = 0.67, p <0.001) and loss of smooth muscle cells (r = -0.68, p <0.001), suggesting that MPO is a relevant source of oxidative stress leading to cell death in the sIA wall. Furthermore, MPO associated with erythrocyte fragmentation (r = 0.74, p <0.001) and iron deposition (p = 0.041), 2 outcomes known to amplify MPO-dependent oxidative stress. Taken together, these results suggest that MPO associates with degenerative remodeling predisposing to sIA wall rupture and may serve as a biomarker of a rupture-prone sIA wall.
  • Ruotsalainen, Anna-Kaisa; Lappalainen, Jari P.; Heiskanen, Emmi; Merentie, Mari; Sihvola, Virve; Näpänkangas, Juha; Lottonen-Raikaslehto, Line; Kansanen, Emilia; Adinolfi, Simone; Kaarniranta, Kai; Ylä-Herttuala, Seppo; Jauhiainen, Matti; Pirinen, Eija; Levonen, Anna-Liisa (2019)
    Aims Oxidative stress and inflammation play an important role in the progression of atherosclerosis. Transcription factor NF-E2-related factor 2 (Nrf2) has antioxidant and anti-inflammatory effects in the vessel wall, but paradoxically, global loss of Nrf2 in apoE deficient mice alleviates atherosclerosis. In this study, we investigated the effect of global Nrf2 deficiency on early and advanced atherogenesis in alternative models of atherosclerosis, LDL receptor deficient mice (LDLR-/-), and LDLR-/- mice expressing apoB-100 only (LDLR-/- ApoB(100/100)) having a humanized lipoprotein profile. Methods and results LDLR-/- mice were fed a high-fat diet (HFD) for 6 or 12weeks and LDLR(-/-)ApoB(100/100) mice a regular chow diet for 6 or 12months. Nrf2 deficiency significantly reduced early and more advanced atherosclerosis assessed by lesion size and coverage in the aorta in both models. Nrf2 deficiency in LDLR-/- mice reduced total plasma cholesterol after 6weeks of HFD and triglycerides in LDLR(-/-)ApoB(100/100) mice on a chow diet. Nrf2 deficiency aggravated aortic plaque maturation in aged LDLR(-/-)ApoB(100/100) mice as it increased plaque calcification. Moreover, approximate to 36% of Nrf2(-/-)LDLR(-/-)ApoB(100/100) females developed spontaneous myocardial infarction (MI) or sudden death at 5 to 12months of age. Interestingly, Nrf2 deficiency increased plaque instability index, enhanced plaque inflammation and calcification, and reduced fibrous cap thickness in brachiocephalic arteries of LDLR(-/-)ApoB(100/100) female mice at age of 12months. Conclusions Absence of Nrf2 reduced atherosclerotic lesion size in both atherosclerosis models, likely via systemic effects on lipid metabolism. However, Nrf2 deficiency in aged LDLR(-/-)ApoB(100/100) mice led to an enhanced atherosclerotic plaque instability likely via increased plaque inflammation and oxidative stress, which possibly predisposed to MI and sudden death.
  • Söderlund, Sanni; Taskinen, Marja-Riitta (2018)
  • Ruuth, Maija; Lahelma, Mari; Luukkonen, Panu K.; Lorey, Martina B.; Qadri, Sami; Sädevirta, Sanja; Hyötyläinen, Tuulia; Kovanen, Petri T.; Hodson, Leanne; Yki-Järvinen, Hannele; Öörni, Katariina (2021)
    OBJECTIVE: We recently showed that measurement of the susceptibility of LDL (low-density lipoprotein) to aggregation is an independent predictor of cardiovascular events. We now wished to compare effects of overfeeding different dietary macronutrients on LDL aggregation, proteoglycan-binding of plasma lipoproteins, and on the concentration of oxidized LDL in plasma, 3 in vitro parameters consistent with increased atherogenicity. APPROACH AND RESULTS: The participants (36 subjects; age, 48±10 years; body mass index, 30.9±6.2 kg/m2) were randomized to consume an extra 1000 kcal/day of either unsaturated fat, saturated fat, or simple sugars (CARB) for 3 weeks. We measured plasma proatherogenic properties (susceptibility of LDL to aggregation, proteoglycan-binding, oxidized LDL) and concentrations and composition of plasma lipoproteins using nuclear magnetic resonance spectroscopy, and in LDL using liquid chromatography mass spectrometry, before and after the overfeeding diets. LDL aggregation increased in the saturated fat but not the other groups. This change was associated with increased sphingolipid and saturated triacylglycerols in LDL and in plasma and reduction of clusterin on LDL particles. Proteoglycan binding of plasma lipoproteins decreased in the unsaturated fat group relative to the baseline diet. Lipoprotein properties remained unchanged in the CARB group. CONCLUSIONS: The type of fat during 3 weeks of overfeeding is an important determinant of the characteristics and functional properties of plasma lipoproteins in humans.
  • Hilvo, Mika; Simolin, Helena; Metso, Jari; Ruuth, Maija; Öörni, Katariina; Jauhiainen, Matti; Laaksonen, Reijo; Baruch, Amos (2018)
    Background and aims: While inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) is known to result in dramatic lowering of LDL-cholesterol (LDL-C), it is poorly understood how it affects other lipid species and their metabolism. The aim of this study was to characterize the alterations in the lipidome of plasma and lipoprotein particles after administration of PCSK9 inhibiting antibody to patients with established coronary heart disease. Methods: Plasma samples were obtained from patients undergoing a randomized placebo-controlled phase II trial (EQUATOR) for the safe and effective use of RG7652, a fully human monoclonal antibody inhibiting PCSK9 function. Lipoprotein fractions were isolated by sequential density ultracentrifugation, and both plasma and major lipoprotein classes (VLDL-IDL, LDL, HDL) were subjected to mass spectrometric lipidomic profiling. Results: PCSK9 inhibition significantly decreased plasma levels of several lipid classes, including sphingolipids (dihydroceramides, glucosylceramides, sphingomyelins, ceramides), cholesteryl esters and free cholesterol. Previously established ceramide ratios predicting cardiovascular mortality, or inflammation related eicosanoid lipids, were not altered. RG7652 treatment also affected the overall and relative distribution of lipids in lipoprotein classes. An overall decrease of total lipid species was observed in LDL and VLDL thorn IDL particles, while HDL-associated phospholipids increased. Following the treatment, LDL displayed reduced lipid cargo, whereas relative lipid proportions of the VLDL thorn IDL particles were mostly unchanged, and there were relatively more lipids carried in the HDL particles. Conclusions: Administration of PCSK9 antibody significantly alters the lipid composition of plasma and lipoprotein particles. These changes further shed light on the link between anti-PCSK9 therapies and cardiovascular risk. (C) 2018 Elsevier B.V. All rights reserved.
  • Koponen, Jaana (Helsingin yliopisto, 2018)
    Tässä syventävässä tutkielmassa selvitettiin tilastollisen analyysin avulla lapsuudessa sairastettujen suusairauksien korrelaatiota aikuisuudessa havaittaviin valtimokovettumataudin riskitekijöihin ja sen vaikeusasteeseen. Tutkielma tehtiin osana lasten ja nuorten sepelvaltimotaudin riskitekijät (LASERI) -tutkimusta. Suusairauksien ja sydäntautien yhteyttä on tutkittu runsaasti ja etenkin parodontiitin on osoitettu lisäävän riskiä valtimokovettumatautiin. Tämä pitkittäistutkimus on kuitenkin ensimmäisiä, jossa tutkitaan lapsuusiän suusairauksien vaikutusta valtimokovettumataudin kehittymiseen. Tärkeimpiä sairauksien välistä yhteyttä selittäviä tekijöitä ovat infektio, inflammaatio ja elimistön immuunijärjestelmän säätelyn häiriintyminen. Käyttämässäni aineistossa 755 lapselle ja nuorelle oli tehty suun terveystarkastus, josta tilastoitiin karies, parodontiitti, gingiviitti, plakin ja hammaskiven määrä sekä hampaiden harjaustiheys. Näitä verrattiin 27 vuotta myöhemmin mitattuihin kaulavaltimon seinämän paksuuteen ja joustavuuteen, olkavarren valtimon virtausvälitteiseen vasodilataatioon, verenpaineeseen, kolesteroliarvoihin, glukoosipitoisuuteen ja painoindeksiin. Korrelaation ja p-arvot saatiin SPSS-ohjelman ANOVA-testin avulla. Gingiviitti korreloi korkean carotiksen intima-media-paksuuden (cIMT), systolisen ja diastolisen verenpaineiden sekä matalan carotiksen komplianssin (cDC) kanssa. Parodontiitti korreloi korkean cIMT:n ja cDC:n kanssa. Karieksella oli tilastollista merkitystä korkeiden systolisen ja diastolisen verenpaineiden kanssa. Plakki korreloi suuren painoindeksin (BMI) sekä korkean systolisen ja diastolisen verenpaineen kanssa. Matala hampaiden harjaustiheys yhdistyi korkeaan diastoliseen verenpaineeseen. Tämän tutkimuksen tulokset viittaavat, että lapsuuden ja nuoruuden aikana sairastetuista suusairauksista parodontaalisairaudet ja karies korreloivat aikuisiällä mitattavan valtimokovettumataudin riskitekijöiden kanssa. (190 sanaa)
  • Strandberg, Timo (2020)
  • Jalkanen, Juho M.; Wickstrom, Jan-Erik; Venermo, Maarit; Hakovirta, Harri H. (2016)
    Background and aims: Several studies report correlation of ankle brachial index (ABI) values and mortality. However, no studies exist on the predictive value of anatomical distribution of atherosclerotic lesions and the extent of atherosclerosis at defined arterial segments on life expectancy. The aim of the present study was to evaluate the significance of both extent and localisation of atherosclerotic lesions to mid-term patient survival. Methods: Digital subtraction angiography (DSA) images of 887 consecutive patients admitted to the Department of Vascular Surgery at Turku University Hospital (Turku, Finland) were retrospectively analysed. Each angiography was classified according to the TASC II classification for aorto-iliac and femoro-popliteal segments, and a similar four-grade index was created for crural arteries. Patients were followed until 36-months post DSA. Results: During 36-month follow-up 295 (33%) deaths occurred. Death during follow-up was strongly associated with extensive crural disease, but not with extensive proximal disease (Crural Index p = 0.044 and <0.001, respectively). In a Cox regression analysis incorporating baseline variables, Crural Index IV and most severe atherosclerosis on crural vessels were the strongest predictors of poor prognosis (HR 2.20 95% CI 1.3-3.7, p = 0.003 and HR 2.45 95% CI 1.5-4.0, p <0.001 respectively). Conclusions: The extent of crural atherosclerosis is independently associated with poor mid term life expectancy. Therefore, a classification of the extent of crural atherosclerosis could serve as an indicator of mortality among PAD patients and aid in clinical decision making. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Kortesoja, Maarit; Taavitsainen, Eveliina; Hanski, Leena (2021)
    Triggered by changes in macrophage redox status and lipid metabolism, foam cells represent a hallmark of atherosclerosis. Induction of macrophage foam cell formation by Chlamydia pneumoniae, a gram-negative human pathogen, has been established in various earlier studies in vitro and in vivo. Oxidation of low-density lipoprotein (LDL) by C. pneumoniae and alterations in macrophage lipid metabolism do not require chlamydial replication, making conventional antibiotics useless in the intervention of the process. In this work, we report on the ability of schisandrin B and schisandrin C, two dibenzocyclooctadiene lignans, to suppress the C. pneumoniae -induced foam cell formation in RAW264.7 macrophages. This effect was accompanied with the upregulation of PPARγ, a nuclear receptor acting as a major transcriptional regulator of lipid metabolism and inflammatory responses. Schisandrin B and schisandrin C also increased the total intracellular glutathione content of the macrophages. In the case of schisandrin B, this was accompanied with the upregulation of GSH biosynthetic genes glutamate cysteine ligase (both the catalytic and the modifier subunits GCLc and GCLm) as well as gamma-glutamyl transpeptidase GGT1. In addition, schisandrin B and schisandrin C upregulated the expression of a lipid transport protein ABCA1 gene mediating cholesterol efflux from macrophages translating into a reduction in total cholesterol concentration in the schisandrin B -treated cells. Collectively, these data indicate that both schisandrin B and schisandrin C are able to alleviate the pathogenic consequences of C. pneumoniae infection in macrophages by altering the cellular redox balance and lipid trafficking.
  • Fromm, Annette; Thomassen, Lars; Naess, Halvor; Meijer, Rudy; Eide, Geir Egil; Krakenes, Jostein; Vedeler, Christian A.; Gerdts, Eva; Larsen, Terje H.; Kuiper, Karel K-J; Laxdal, Elin; Russell, David; Tatlisumak, Turgut; Waje-Andreassen, Ulrike (2013)
  • Strandberg, Timo; Syvänne, Mikko (2018)
  • Tulamo, Riikka; Mäyränpää, Mikko I.; Aho, Pekka (2019)