Browsing by Subject "ATHEROSCLEROSIS"

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  • Kaijasilta, Juha-Pekka; Kerola, Anne M.; Tuompo, Riitta; Relas, Heikki; Loimaala, Antti; Koivu, Hannu; Schildt, Jukka; Kerola, Tuomas; Eklund, Kari; Kauppi, Markku J.; Nieminen, Tuomo V.M. (2022)
    Aim: Inflammatory signals in the sacroiliac (SI) joints and the aorta of patients with axial spondyloarthritis (axSpA) were graded by positron emission tomography/computed tomography (PET/CT) imaging before and after treatment with sulfasalazine (SSZ) or adalimumab (ADA). Methods: Patients with axSpA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, were recruited. Disease-modifying antirheumatic drug-naïve patients started SSZ for 12 weeks, whereas those with prestudy treatment with or contraindication to SSZ commenced ADA for 16 weeks. In addition, those patients in the SSZ group with insufficient response commenced ADA for 16 weeks. 18F-fluorodeoxyglucose PET/CT was performed after inclusion and after treatment with SSZ and ADA. Maximum standardized uptake value (SUVmax) was assessed for the aorta and the SI joints, and maximal target-to-blood-pool ratio (TBRmax) only for the aorta. Results: Among five SSZ patients, mean ± SD BASDAI was 4.7 ± 1.6 before and 3.5 ± 1.4 after treatment (p =.101). In 13 ADA patients, the BASDAI decreased from 5.4 ± 1.6 to 2.8 ± 2.2 (p <.001). Among the SSZ patients, SUVmax in SI joints decreased from 2.35 ± 0.55 to 1.51 ± 0.22 (−35.8%, p =.029). Aortic TBRmax decreased from 1.59 ± 0.43 to 1.26 ± 0.26 (−33.2%, p =.087). In the ADA patients, SUVmax in the SI joints was 1.92 ± 0.65 before and 1.88 ± 0.54 after treatment (−1.8%, p =.808) and TBRmax in the aorta 1.50 ± 0.60 before and 1.40 ± 0.26 after treatment (−6.7%, p =.485). Conclusions: Our small open-label study showed that SSZ may reduce PET-CT-detectable inflammation in the SI joints, with a trend towards a reduction in the aorta.
  • Inouye, Michael; Silander, Kaisa; Hämäläinen, Eija; Salomaa, Veikko; Harald, Kennet; Jousilahti, Pekka; Mannisto, Satu; Eriksson, Johan G.; Saarela, Janna; Ripatti, Samuli; Perola, Markus; van Ommen, Gert-Jan B.; Taskinen, Marja-Riitta; Palotie, Aarno; Dermitzakis, Emmanouil T.; Peltonen, Leena (2010)
  • Karjalainen, Minna K.; Holmes, Michael V.; Wang, Qin; Anufrieva, Olga; Kähönen, Mika; Lehtimäki, Terho; Havulinna, Aki S.; Kristiansson, Kati; Salomaa, Veikko; Perola, Markus; Viikari, Jorma S.; Raitakari, Olli T.; Järvelin, Marjo-Riitta; Ala-Korpela, Mika; Kettunen, Johannes (2020)
    Background and aims: Apolipoprotein A-I (apoA-I) infusions represent a potential novel therapeutic approach for the prevention of coronary artery disease (CAD). Although circulating apoA-I concentrations inversely associate with risk of CAD, the evidence base of this representing a causal relationship is lacking. The aim was to assess the causal role of apoA-I using human genetics. Methods: We identified a variant (rs12225230) in APOA1 locus that associated with circulating apoA-I concentrations (p <5 x 10(-8)) in 20,370 Finnish participants, and meta-analyzed our data with a previous GWAS of apoA-I. We obtained genetic estimates of CAD from UK Biobank and CARDIoGRAMplusC4D (totaling 122,733 CAD cases) and conducted a two-sample Mendelian randomization analysis. We compared our genetic findings to observational associations of apoA-I with risk of CAD in 918 incident CAD cases among 11,535 individuals from population-based prospective cohorts. Results: ApoA-I was associated with a lower risk of CAD in observational analyses (HR 0.81; 95%CI: 0.75, 0.88; per 1-SD higher apoA-I), with the association showing a dose-response relationship. Rs12225230 associated with apoA-I concentrations (per-C allele beta 0.076 SD; SE: 0.013; p = 1.5 x 10(-9)) but not with confounders. In Mendelian randomization analyses, apoA-I was not related to risk of CAD (OR 1.13; 95%CI: 0.98,1.30 per 1-SD higher apoA-I), which was different from the observational association. Similar findings were observed using an independent ABCA1 variant in sensitivity analysis. Conclusions: Genetic evidence fails to support a cardioprotective role for apoA-I. This is in line with the cumulative evidence showing that HDL-related phenotypes are unlikely to have a protective role in CAD.
  • Takatalo, Jani; Karppinen, Jaro; Taimela, Simo; Niinimaki, Jaakko; Laitinen, Jaana; Sequeiros, Roberto Blanco; Samartzis, Dino; Korpelainen, Raija; Nayha, Simo; Remes, Jouko; Tervonen, Osmo (2013)
  • Halonen, Jaana I.; Dehbi, Hakim-Moulay; Hansell, Anna L.; Gulliver, John; Fecht, Daniela; Blangiardo, Marta; Kelly, Frank J.; Chaturvedi, Nish; Kivimaki, Mika; Tonne, Cathryn (2017)
    Background: Road traffic noise has been linked to increased risk of stroke, for which hypertension and carotid intima-media thickness (cIMT) are risk factors. A link between traffic noise and hypertension has been established, but there are few studies on blood pressure and no studies on cIMT. Objectives: To examine cross-sectional associations for long-term exposure to night-time noise with cIMT, systolic blood pressure (SBP), diastolic blood pressure (DBP) and hypertension. Methods: The study population consisted of 2592 adults from the Whitehall II and SABRE cohort studies living within Greater London who had cIMT, SBP and DBP measured. Exposure to night-time road traffic noise (A-weighted dB, referred to as dBA) was estimated at each participant's residential postcode centroid. Results: Mean night-time road noise levels were 52 dBA (SD=4). In the pooled analysis adjusted for cohort, sex, age, ethnicity, marital status, smoking, area-level deprivation and NOx there was a 9.1 mu m (95% CI: -7.1, 25.2) increase in cIMT in association with 10 dBA increase in night-time noise. Analyses by noise categories of 5560 dBA (16.2 mu m, 95% CI:-8.7, 41.2), and N60 dBA (21.2 mu m, 95% CI:-2.5, 44.9) vs. 60 dBA vs. Conclusions: After adjustments, including for air pollution, the association between night-time road traffic noise and cIMT was only observed among non-medication users but associations with blood pressure and hypertension were largely null. (C) 2016 Elsevier Ltd. All rights reserved.
  • Simonsen, Johan Rasmus; Järvinen, Asko; Hietala, Kustaa; Harjutsalo, Valma; Forsblom, Carol; Groop, Per-Henrik; Lehto, Markku (2021)
    Background/Aims Diabetic retinopathy (DR) is associated and shares many risk factors with other diabetic complications, including inflammation. Bacterial infections, potent inducers of inflammation have been associated with the development of diabetic complications apart from DR. Our aim was to investigate the association between bacterial infections and DR. Methods Adult individuals with type 1 diabetes (n=1043) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. DR was defined as incident severe diabetic retinopathy (SDR), identified as first laser treatment. Data on DR were obtained through fundus photographs and medical records, data on bacterial infections from comprehensive national registries (1 January 1995 to 31 December 2015). Risk factors for DR and serum bacterial lipopolysaccharide (LPS) activity were determined at baseline. Results Individuals with incident SDR (n=413) had a higher mean number of antibiotic purchases/follow-up year compared with individuals without incident SDR (n=630) (0.92 [95% CI 0.82 to 1.02] vs 0.67 [0.62-0.73], p=0.02), as well as higher levels of LPS activity (0.61 [0.58-0.65] vs 0.56 [0.54-0.59] EU/mL, p=0.03). Individuals with on average >= 1 purchase per follow-up year (n=269) had 1.5 times higher cumulative incidence of SDR, compared with individuals with
  • Castelblanco, Esmeralda; Sarrias, Maria R.; Betriu, Angels; Soldevila, Berta; Barranco-Altirriba, Maria; Franch-Nadal, Josep; Valdivielso, Jose M.; Bermudez-Lopez, Marcelino; Groop, Per-Henrik; Fernandez, Elvira; Alonso, Nuria; Mauricio, Didac (2021)
    This study assessed the association of CD5L and soluble CD36 (sCD36) with the risk of a cardiovascular event (CVE), including CV death and all-cause mortality in CKD. We evaluated the association of CD5L and sCD36 with a predefined composite CV endpoint (unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular accident, congestive heart failure, arrhythmia, peripheral arterial disease [PAD] or amputation by PAD, aortic aneurysm, or death from CV causes) and all-cause mortality using Cox proportional hazards regression, adjusted for CV risk factors. The analysis included 1,516 participants free from pre-existing CV disease followed up for 4 years. The median age was 62 years, 38.8% were female, and 26.8% had diabetes. There were 98 (6.5%) CVEs and 72 (4.8%) deaths, of which 26 (36.1%) were of CV origin. Higher baseline CD5L concentration was associated with increased risk of CVE (HR, 95% CI, 1.17, 1.0-1.36), and all-cause mortality (1.22, 1.01-1.48) after adjusting for age, sex, diabetes, systolic blood pressure, dyslipidemia, waist circumference, smoking, and CKD stage. sCD36 showed no association with adverse CV outcomes or mortality. Our study showed for the first time that higher concentrations of CD5L are associated with future CVE and all -cause mortality in individuals with CKD.
  • Latorre, Jèssica; Ortega, Francisco J.; Liñares-Pose, Laura; Moreno-Navarrete, José M.; Lluch, Aina; Comas, Ferran; Oliveras-Cañellas, Núria; Ricart, Wifredo; Höring, Marcus; Zhou, You; Liebisch, Gerhard; Nidhina Haridas, P.A.; Olkkonen, Vesa M.; López, Miguel; Fernández-Real, José M. (2020)
    Background: While the impact of metformin in hepatocytes leads to fatty acid (FA) oxidation and decreased lipogenesis, hepatic microRNAs (miRNAs) have been associated with fat overload and impaired metabolism, contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Methods: We investigated the expression of hundreds of miRNAs in primary hepatocytes challenged by compounds modulating steatosis, palmitic acid and compound C (as inducers), and metformin (as an inhibitor). Then, additional hepatocyte and rodent models were evaluated, together with transient mimic miRNAs transfection, lipid droplet staining, thin-layer chromatography, quantitative lipidomes, and mitochondrial activity, while human samples outlined the translational significance of this work. Findings: Our results show that treatments triggering fat accumulation and AMPK disruption may compromise the biosynthesis of hepatic miRNAs, while the knockdown of the miRNA-processing enzyme DICER in human hepatocytes exhibited increased lipid deposition. In this context, the ectopic recovery of miR-30b and miR-30c led to significant changes in genes related to FA metabolism, consistent reduction of ceramides, higher mitochondrial activity, and enabled b-oxidation, redirecting FA metabolism fromenergy storage to expenditure. Interpretation: Current findings unravel the biosynthesis of hepatic miR-30b and miR-30c in tackling inadequate FA accumulation, offering a potential avenue for the treatment of NAFLD. Funding: Instituto de Salud Carlos III (ISCIII), Govern de la Generalitat (PERIS2016), Associacio Catalana de Diabetis (ACD), Sociedad Espanola de Diabetes (SED), Fondo Europeo de Desarrollo Regional (FEDER), Xunta de Galicia, Ministerio de Economia y Competitividad (MINECO), "La Caixa" Foundation, and CIBER de la Fisiopatologia de la Obesidad y Nutricion (CIBEROBN). (c) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
  • Uusitalo, Valtteri; Kamperidis, Vasileios; de Graaf, Michiel A.; Maaniitty, Teemu; Stenstrom, Iida; Broersen, Alexander; Dijkstra, Jouke; Scholte, Arthur J.; Saraste, Antti; Bax, Jeroen J.; Knuuti, Juhani (2017)
    Background: We evaluated the prognostic value of an integrated atherosclerosis risk score combining the markers of coronary plaque burden, location and composition as assessed by computed tomography angiography (CTA). Methods: 922 consecutive patients underwent CTA for suspected coronary artery disease (CAD). Patients without atherosclerosis (n = 261) and in whom quantitative CTA analysis was not feasible due to image quality, step-artefacts or technical factors related to image acquisition or data storage (n = 153) were excluded. Thus, final study group consisted of 508 patients aged 63 9 years. Coronary plaque location, severity and composition for each coronary segment were identified using automated CTA quantification software and integrated in a single CTA score (0-42). Adverse events (AE) including death, myocardial infarction (MI) and unstable angina (UA) were obtained from the national healthcare statistics. Results: There were a total of 20 (4%) AE during a median follow-up of 3.6 years (9 deaths, 5 MI and 6 UA). The CTA risk score was divided into tertiles: 0-6.7, 6.8-14.8 and > 14.8, respectively. All MI (n = 5) and most of the other AE occurred in the highest risk score tertile (3 vs. 3 vs. 14, p = 0.002). After correction for age and gender, the CTA risk score remained independently associated with AE. Conclusions: Comprehensive CIA risk score integrating the location, burden and composition of coronary atherosclerosis predicts future cardiac events in patients with suspected CAD. (C) 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.
  • Ohukainen, Pauli; Kuusisto, Sanna; Kettunen, Johannes; Perola, Markus; Järvelin, Marjo-Riitta; Makinen, Ville-Petteri; Ala-Korpela, Mika (2020)
    Background and aims: Population subgrouping has been suggested as means to improve coronary heart disease (CHD) risk assessment. We explored here how unsupervised data-driven metabolic subgrouping, based on comprehensive lipoprotein subclass data, would work in large-scale population cohorts. Methods: We applied a self-organizing map (SOM) artificial intelligence methodology to define subgroups based on detailed lipoprotein profiles in a population-based cohort (n = 5789) and utilised the trained SOM in an independent cohort (n = 7607). We identified four SOM-based subgroups of individuals with distinct lipoprotein profiles and CHD risk and compared those to univariate subgrouping by apolipoprotein B quartiles. Results: The SOM-based subgroup with highest concentrations for non-HDL measures had the highest, and the subgroup with lowest concentrations, the lowest risk for CHD. However, apolipoprotein B quartiles produced better resolution of risk than the SOM-based subgroups and also striking dose-response behaviour. Conclusions: These results suggest that the majority of lipoprotein-mediated CHD risk is explained by apolipoprotein B-containing lipoprotein particles. Therefore, even advanced multivariate subgrouping, with comprehensive data on lipoprotein metabolism, may not advance CHD risk assessment
  • Soder, Birgitta; Meurman, Jukka H.; Soder, Per-Osten (2014)
  • Soder, Birgitta; Meurman, Jukka H.; Soder, Per-Osten (2016)
    Objectives Dental infections, such as periodontitis, associate with atherosclerosis and its complications. We studied a cohort followed-up since 1985 for incidence of angina pectoris with the hypothesis that calculus accumulation, proxy for poor oral hygiene, links to this symptom. Methods In our Swedish prospective cohort study of 1676 randomly selected subjects followed-up for 26 years. In 1985 all subjects underwent clinical oral examination and answered a questionnaire assessing background variables such as socio-economic status and pack-years of smoking. By using data from the Center of Epidemiology, Swedish National Board of Health and Welfare, Sweden we analyzed the association of oral health parameters with the prevalence of in-hospital verified angina pectoris classified according to the WHO International Classification of Diseases, using descriptive statistics and logistic regression analysis. Results Of the 1676 subjects, 51 (28 women/23 men) had been diagnosed with angina pectoris at a mean age of 59.8 +/- 2.9 years. No difference was observed in age and gender between patients with angina pectoris and subjects without. Neither was there any difference in education level and smoking habits (in pack years), Gingival index and Plaque index between the groups. Angina pectoris patients had significantly more often their first maxillary molar tooth extracted (d. 16) than the other subjects (p = 0.02). Patients also showed significantly higher dental calculus index values than the subjects without angina pectoris (p = 0.01). Multiple regression analysis showed odds ratio 2.21 (95% confidence interval 1.17-4.17) in the association between high calculus index and angina pectoris (p = 0.015). Conclusion Our study hypothesis was confirmed by showing for the first time that high dental calculus score indeed associated with the incidence of angina pectoris in this cohort study.
  • Elfving, P.; Puolakka, K.; Kautiainen, H.; Virta, L. J.; Pohjolainen, T.; Kaipiainen-Seppanen, O. (2016)
    The objectives of the study were to examine the initial, first-year anti-rheumatic outpatient therapy in patients with incident SLE, as well as the concomitant use of drugs for certain comorbidities, compared to the use in the general population. The Finnish nationwide register data on special reimbursements for medication costs was screened to identify the inception cohort of 566 adult SLE patients (87% females, mean age 46.5 +/- 15.9 years) over the years 2000-2007. The patients were linked to the national Drug Purchase Register. Of those, 90% had purchased at least once some disease-modifying anti-rheumatic drugs (DMARDs) during the first year. Hydroxychloroquine was the most common (76%), followed by azathioprine (15%) and methotrexate (13%). With the exception of increase in mycophenolate mofetil, the proportions remained stable over the whole study period 2000-2007. Drugs for cardiovascular diseases, dyslipidemia, diabetes mellitus, hypothyroidism and obstructive pulmonary disease were more frequently purchased than in the sex- and age-adjusted population, with rate ratios ranging from 1.6 to 7.8. Over the years 2000-2007, almost all the patients with incident SLE in Finland started with a DMARD. Higher percentages of SLE patients were on medication for several common chronic diseases than in the population as a whole.
  • Matikainen, Niina; Burza, Maria Antonella; Romeo, Stefano; Hakkarainen, Antti; Adiels, Martin; Folkersen, Lasse; Eriksson, Per; Lundbom, Nina; Ehrenborg, Ewa; Orho-Melander, Marju; Taskinen, Marja-Riitta; Boren, Jan (2013)
  • Chiesa, Scott T.; Charakida, Marietta; Georgiopoulos, Georgios; Roberts, Justin D.; Stafford, Simon J.; Park, Chloe; Mykkanen, Juha; Kahonen, Mika; Lehtimaki, Terho; Ala-Korpela, Mika; Raitakari, Olli; Pietiäinen, Milla; Pussinen, Pirkko; Muthurangu, Vivek; Hughes, Alun D.; Sattar, Naveed; Timpson, Nicholas J.; Deanfield, John E. (2022)
    Background Low-grade inflammation in the young may contribute to the early development of cardiovascular disease. We assessed whether circulating levels of glycoprotein acetyls (GlycA) were better able to predict the development of adverse cardiovascular disease risk profiles compared with the more commonly used biomarker high-sensitivity CRP (C-reactive protein). Methods and Results A total of 3306 adolescents and young adults from the Avon Longitudinal Study of Parents and Children (mean age, 15.4 +/- 0.3; n=1750) and Cardiovascular Risk in Young Finns Study (mean age, 32.1 +/- 5.0; n=1556) were included. Baseline associations between inflammatory biomarkers, body composition, cardiovascular risk factors, and subclinical measures of vascular dysfunction were assessed cross-sectionally in both cohorts. Prospective risk of developing hypertension and metabolic syndrome during 9-to-10-year follow-up were also assessed as surrogate markers for future cardiovascular risk. GlycA showed greater within-subject correlation over 9-to-10-year follow-up in both cohorts compared with CRP, particularly in the younger adolescent group (r=0.36 versus 0.07). In multivariable analyses, GlycA was found to associate with multiple lifestyle-related cardiovascular disease risk factors, cardiometabolic risk factor burden, and vascular dysfunction (eg, mean difference in flow-mediated dilation=-1.2 [-1.8, -0.7]% per z-score increase). In contrast, CRP levels appeared predominantly driven by body mass index and showed little relationship to any measured cardiovascular risk factors or phenotypes. In both cohorts, only GlycA predicted future risk of both hypertension (risk ratio [RR], approximate to 1.1 per z-score increase for both cohorts) and metabolic syndrome (RR, approximate to 1.2-1.3 per z-score increase for both cohorts) in 9-to-10-year follow-up. Conclusions Low-grade inflammation captured by the novel biomarker GlycA is associated with adverse cardiovascular risk profiles from as early as adolescence and predicts future risk of hypertension and metabolic syndrome in up to 10-year follow-up. GlycA is a stable inflammatory biomarker which may capture distinct sources of inflammation in the young and may provide a more sensitive measure than CRP for detecting early cardiovascular risk.
  • Korpijaakko, Cedric A.; Eriksson, Mia D.; Wasenius, Niko S.; Klemetti, Miira M.; Teramo, Kari; Kautiainen, Hannu; Eriksson, Johan G.; Laine, Merja K. (2022)
    Background Offspring of mothers with type 1 diabetes have an increased risk for acquiring early onset cardiovascular disease (CVD). Arterial stiffness, measured as pulse wave velocity (PWV), is a non-invasive biomarker for CVD risk assessment. Our aim is to determine whether PWV is increased in young adult offspring of mothers with type 1 diabetes. Methods This is a case-control study carried out in the hospital district of Helsinki and Uusimaa, Finland. 75 offspring of mothers with type 1 diabetes (cases) and 84 offspring of mothers without diabetes (controls), aged 18-23 years, were enrolled in this study. All participants attended clinical assessments, including questionnaires and laboratory tests. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and PWV ratio were measured from each participant using the Complior Analyse mechanotransducer (Alam Medical, France). Student's t-test and chi-squared test were used to assess differences between the groups. Stata 17.0, StataCorp LP (College Station, TX, USA) statistical package was used for the analysis. Results We did not observe any differences in conventional CVD risk factors: systolic blood pressure, LDL, Hb(A1c), and smoking between cases and controls. We detected higher cfPWV in cases 6.5 (SD +/- 1.2) m/s than in controls 6.2 (SD +/- 0.7) m/s, p = 0.049, after adjustments for BMI, smoking, mean arterial pressure, height, and pulse rate was made. We did not observe any difference between cases and controls regarding crPWV or PWV ratio. Additionally, we detected no sex differences. Conclusions We report a novel finding of signs of increased arterial stiffness already in young adult offspring of mothers with type 1 diabetes compared to matched offspring of mothers without diabetes. Our finding suggests that exposure to an adverse intrauterine environment of type 1 diabetes mothers may affect the vascular health of offspring already in young adulthood. Additional research within this topic is warranted.
  • Gungor, Burcin; Vanharanta, Lauri; Hölttä-Vuori, Maarit; Pirhonen, Juho; Petersen, Nikolaj H. T.; Gramolelli, Silvia; Ojala, Päivi M.; Kirkegaard, Thomas; Ikonen, Elina (2019)
    Objective: Heat Shock Proteins (HSPs) maintain cellular homeostasis under stress. HSP70 represents a major stress-inducible family member and has been identified as a druggable target in inherited cholesterol-sphingolipid storage diseases. We investigated if HSP70 modulates cholesterol accumulation in more common conditions related to atherogenesis. Methods: We studied the effects of recombinant HSP70 in cholesterol-laden primary macrophages from human blood donors and pharmacological HSP70 upregulation in high-cholesterol diet fed zebrafish. Results: Recombinant HSP70 facilitated cholesterol removal from primary human macrophage foam cells. RNA sequencing revealed that HSP70 induced a robust transcriptional re-programming, including upregulation of key targets of liver X receptors (LXR), master regulators of whole-body cholesterol removal. Mechanistically, HSP70 interacted with the macrophage LXRalpha promoter, increased LXRalpha and its target mRNAs, and led to elevated levels of key proteins facilitating cholesterol efflux, including ATP-binding cassette transporters A1 and G1. Pharmacological augmentation of endogenous HSP70 in high-cholesterol diet fed zebrafish activated LXR and its target mRNAs and reduced cholesterol storage at the whole organism level. Conclusion: These data demonstrate that HSP70 exerts a cholesterol lowering effect in primary human cells and animals and uncover a nuclear action of HSP70 in mediating cross-talk between HSP and LXR transcriptional regulation. (C) 2019 The Authors. Published by Elsevier GmbH.
  • Kyrklund, Mikael; Bildo, Mika; Akhi, Ramin; Nissinen, Antti E.; Pussinen, Pirkko; Hörkkö, Sohvi; Wang, Chunguang (2020)
    Atherosclerosis is a chronic inflammatory disease and major cause of mortality worldwide. One of the crucial steps for atherosclerotic plaque development is oxidation of low-density lipoprotein (LDL). Through the oxidation, highly immunogenic epitopes are created and the immune system is activated. Association between atherosclerosis and periodontal diseases is well documented, and one of the main oral pathogens common in periodontitis is Aggregatibacter actinomycetemcomitans (Aa). Heat shock protein 60 (HSP60) is an important virulence factor for Aa bacteria and a strong activator of the immune system. Cross-reactivity of HSP60 and oxidized LDL (OxLDL) antibodies could be a potential mechanism in the progression of atherosclerosis and one possible link between atherosclerosis and periodontitis. Human plasma samples from neonates and mothers were analyzed to determine if antibody titer to Aa-HSP60 protein is already present in newborns. Further objectives were to characterize antibody response in Aa-HSP60 immunized mice and to determine possible antibody cross-reaction with oxidized LDL. We demonstrated that newborns already have IgM antibody levels to Aa-HSP60. We also showed that in mice, Aa-HSP60 immunization provoked IgG and IgM antibody response not only to Aa-HSP60 but also to malondialdehyde acetaldehyde-modified LDL (MAA-LDL). Competition assay revealed that the antibodies were specific to Aa-HSP60 and cross-reacted with MAA-LDL. Our results suggest a possibility of molecular mimicry between Aa-HSP60 and MAA-LDL, making it intriguing to speculate on the role of HSP60 protein in atherosclerosis that manifests at young age.