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3. Variation in secondary prevention of coronary heart disease: the INTERASPIRE study.

Author

McEvoy, John William, Jennings, Catriona, Kotseva, Kornelia, Bacquer, Dirk De, Backer, Guy De, Erlund, Iris, Vihervaara, Terhi, Lip, Gregory Y H, Ray, Kausik K, Rydén, Lars, Abreu, Ana, Almahmeed, Wael, Ambari, Ade Meidian, Ge, Junbo, Hasan-Ali, Hosam, Huo, Yong, Jankowski, Piotr, Jimenez, Rodney M, Li, Yong, and Zuhdi, Ahmad Syadi Mahmood

Subjects
CORONARY disease, SECONDARY prevention, LDL cholesterol, HEALTH equity, CARDIAC rehabilitation
Abstract

Background and Aims INTERASPIRE is an international study of coronary heart disease (CHD) patients, designed to measure if guideline standards for secondary prevention and cardiac rehabilitation are being achieved in a timely manner. Methods Between 2020 and 2023, adults hospitalized in the preceding 6–24 months with incident or recurrent CHD were sampled in 14 countries from all 6 World Health Organization regions and invited for a standardized interview and examination. Direct age and sex standardization was used for country-level prevalence estimation. Results Overall, 4548 (21.1% female) CHD patients were interviewed a median of 1.05 (interquartile range.76–1.45) years after index hospitalization. Among all participants, 24.6% were obese (40.7% centrally). Only 38.6% achieved a blood pressure (BP) < 130/80 mmHg and 16.6% a LDL cholesterol (LDL-C) of <1.4 mmol/L. Of those smoking at hospitalization, 48% persisted at interview. Of those with known diabetes, 55.2% achieved glycated haemoglobin (HbA1c) of <7.0%. A further 9.8% had undetected diabetes and 26.9% impaired glucose tolerance. Females were less likely to achieve the targets: BP (females 36.8%, males 38.9%), LDL-C (females 12.0%, males 17.9%), and HbA1c in diabetes (females 47.7%, males 57.5%). Overall, just 9.0% (inter-country range 3.8%–20.0%) reported attending cardiac rehabilitation and 1.0% (inter-country range.0%–2.4%) achieved the study definition of optimal guideline adherence. Conclusions INTERASPIRE demonstrates inadequate and heterogeneous international implementation of guideline standards for secondary prevention in the first year after CHD hospitalization, with geographic and sex disparity. Investment aimed at reducing between-country and between-individual variability in secondary prevention will promote equity in global efforts to reduce the burden of CHD. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Serum ferritin level is associated with liver fibrosis and incident liver-related outcomes independent of HFE genotype in the general population.

Author

Männistö, Ville T., Hakkarainen, Konsta, Jula, Antti, Lundqvist, Annamari, Vihervaara, Terhi, Erlund, Iris, and Åberg, Fredrik

Subjects
HEPATIC fibrosis, FERRITIN, IRON in the body, METABOLIC disorders, BODY mass index
Abstract

Hyperferritinemia reflects iron accumulation in the body and has been associated with metabolic disturbances and alcohol use, and is also a common finding in individuals diagnosed with liver disease. The major genetic regulator of iron metabolism is the HFE gene. The aim of this this study was to investigate the association between serum ferritin and liver fibrosis using the enhanced liver fibrosis (ELF) test, and the association between ferritin and liver-related outcomes in a Finnish population-based cohort of 6194 individuals (45% male, mean [± standard deviation] age, 52.9 ± 14.9 years; body mass index 26.9 ± 4.7 kg/m2). The effects of HFE variants on these associations were also evaluated. Serum ferritin levels were significantly associated with liver fibrosis, as estimated by enhanced liver fibrosis (ELF) test in weighted linear regression analysis. Serum ferritin was significantly associated with both all liver-related outcomes (n = 92) and severe liver-related outcomes (n = 54) in weighted Cox regression analysis (hazard ratio [HR] per 1 SD, 1.11 [95% confidence interval (CI) 1.02–1.21]; p = 0.012 and HR 1.11 [95% CI 1.02–1.21]; p = 0.013, respectively). However, there was association neither between HFE risk variants and ELF test nor between HFE risk variants and liver-related outcomes. Serum ferritin levels were associated with liver fibrosis and incident liver disease, independent of HFE genotype in the general population. Furthermore, data demonstrated that metabolic disturbances and alcohol use were major risk factors for hyperferritinemia. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome: Results of the ATHEROREMO-IVUS study

Author

Cheng, Jin M., Suoniemi, Matti, Kardys, Isabella, Vihervaara, Terhi, de Boer, Sanneke P.M., Akkerhuis, K. Martijn, Sysi-Aho, Marko, Ekroos, Kim, Garcia-Garcia, Hector M., Oemrawsingh, Rohit M., Regar, Evelyn, Koenig, Wolfgang, Serruys, Patrick W., van Geuns, Robert-Jan, Boersma, Eric, and Laaksonen, Reijo

Published
2015
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9. Combined use of the ELF test and CLivD score improves prediction of liver‐related outcomes in the general population.

Author

Åberg, Fredrik, Saarinen, Kustaa, Jula, Antti, Lundqvist, Annamari, Vihervaara, Terhi, Erlund, Iris, and Färkkilä, Martti

Subjects
HEPATIC fibrosis, DISEASE risk factors, MONOGENIC & polygenic inheritance (Genetics), HEPATOCELLULAR carcinoma, TEST scoring
Abstract

Background and Aims: Effective and feasible population screening strategies are needed for the early detection of individuals at high risk of future severe liver‐related outcomes. We evaluated the predictive performance of the combination of liver fibrosis assessment, phenotype profile, and genetic risk. Methods: Data from 5795 adults attending the Finnish Health 2000 Survey were linked with healthcare registers for liver‐related outcomes (hospitalization, hepatocellular cancer, and death). Fibrosis was assessed using the enhanced liver fibrosis (ELF) test, phenotype profile by the chronic liver disease (CLivD) risk score, and genetic risk by a validated Polygenic Risk Score (PRS‐5). Predictive performance was assessed by competing‐risk analyses. Results: During a median 13‐year follow‐up, 64 liver‐related outcome events were recorded. ELF, CLivD score, and PRS‐5 were independently associated with liver‐related outcomes. The absolute 10‐year risk of liver‐related outcomes at an ELF value of 11.3 ranged from 0.3% to 33% depending on the CLivD score. The CLivD score added 51% of new predictive information to the ELF test and improved areas under the curve (AUCs) from 0.91, 0.81, and 0.71 for ELF alone to 0.95, 0.85, and 0.80, respectively, for ELF combined with the CLivD score at 1, 5, and 10 years. The greatest improvement was for 10‐year predictions (delta‐AUC 0.097, p <.0001). Adding PRS‐5 did not significantly increase predictive performance. Findings were consistent in individuals with obesity, diabetes, or alcohol risk use, and regardless of whether gamma‐glutamyltransferase was used in the CLivD score. Conclusion: A combination of ELF and CLivD score predicts liver‐related outcomes significantly better than the ELF test alone. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Measures of Insulin Resistance as a Screening Tool for Dysglycemia in Patients With Coronary Artery Disease: A Report From the EUROASPIRE V Population

Author

Ferrannini, Giulia, primary, De Bacquer, Dirk, additional, Erlund, Iris, additional, Gyberg, Viveca, additional, Kotseva, Kornelia, additional, Mellbin, Linda, additional, Norhammar, Anna, additional, Schnell, Oliver, additional, Tuomilehto, Jaakko, additional, Vihervaara, Terhi, additional, Wood, David, additional, and Rydén, Lars, additional

Published
2022
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16. Meta-analysis of the clinical performance of commercial SARS-CoV-2 nucleic acid and antibody tests up to 22 August 2020

Author

Van Walle, Ivo, Leitmeyer, Katrin, Broberg, Eeva K, Van Esbroeck, Marjan, Beuselinck, Kurt, Vermeersch, Pieter, Karagiannis, Christos, Mentis, Andreas, Lampropoulou, Stavroula, Erlund, Iris, Melin, Merit, Ekström, Nina, Vihervaara, Terhi, Gaymard, Alexandre, Frobert, Emilie, Escuret, Vanessa, Kurolt, Ivan-Christian, Fournier, Guillaume, Abdelrahman, Tamir, Nguyen, Trung, Klak, Adrian, Bos, Anne E, Russcher, Anne, van ’t Veen, Annemarie, Stemerding, Annette M, van Corteveen-Splinter, Annette, van Hees, Babette C, Wintermans, Bas B, Herpers, Bjorn L, Reusken, Chantal BEM, van der Donk, Christel FM, Oliveira dos Santos, Claudy, GeurtsvanKessel, Corine H, Timmerman, Cornelis P, Ong, David SY, Kaersenhout, Deborah J, van Lochem, Ellen, Geeraedts, Felix, Rijkers, Ger T, Berkhout, Hannke, Koeleman, Hans GM, van Loo, Inge HM, Rahamat-Langendoen, Janette, Murk, Jean-Luc, Tjhie, Jeroen HT, Kissing, Johan, Reimerink, Johan, Kerremans, Jos J, de Vries, Jutte JC, Heemstra, Karen A, Thai, Khoa TD, Jim, Kin Ki, Mulder, Leontine, van den Beld, Maaike JC, Batstra, Manou R, Konstantinovski, Maria M, Wegdam-Blans, Marjolijn CA, Hoogewerf, Martine, de Graaf, Melanie J, de Jong, Menno D., Heron, Michiel, van Rijn, Michiel, Heusinkveld, Moniek, Van Burgel, Nathalie, Savelkoul, Paul HM, den Reijer, Paul Martijn, Wever, Peter C, Croughs, Peter, Zonneveld, Rens, van Gyseghem, Sim, Thijsen, Steven FT, Stoof, Susanne P, Jurriaans, Suzanne, Debast, Sylvia B, Mank, Theo, Hira, Vishal, Michalski, Aleksander, Siewierska-Puchlerska, Anna, Gajda, Ewa, Paciorek, Jarosław, Pakieła, Marta, Kołakowska-Kulesza, Agnieszka, Pancer, Katarzyna, Nowakowska, Magdalena, Costa, Inês, Zé-Zé, Líbia, Guiomar, Raquel, Hammas, Berit, Öckinger, Johan Brynedal, Prosenc, Katarina, and Berginc, Nataša

Subjects
Infecções Respiratórias, medicine.medical_specialty, Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), diagnostic, specificity, Sensitivity and Specificity, Gastroenterology, Asymptomatic, Nucleic Acids, Virology, Internal medicine, medicine, Humans, media_common.cataloged_instance, European union, Pandemics, media_common, Infecções Sistémicas e Zoonoses, accuracy, biology, SARS-CoV-2, business.industry, Research, Public Health, Environmental and Occupational Health, COVID-19, sensitivity, Confidence interval, meta-analysis, Study heterogeneity, Meta-analysis, biology.protein, Nucleic acid, Antibody Tests, Antibody, medicine.symptom, business
Abstract

Background Reliable testing for SARS-CoV-2 is key for the management of the COVID-19 pandemic. Aim We estimate diagnostic accuracy for nucleic acid and antibody tests 5 months into the COVID-19 pandemic, and compare with manufacturer-reported accuracy. Methods We reviewed the clinical performance of SARS-CoV-2 nucleic acid and antibody tests based on 93,757 test results from 151 published studies and 20,205 new test results from 12 countries in the European Union and European Economic Area (EU/EEA). Results Pooling the results and considering only results with 95% confidence interval width ≤ 5%, we found four nucleic acid tests, including one point-of-care test and three antibody tests, with a clinical sensitivity ≥ 95% for at least one target population (hospitalised, mild or asymptomatic, or unknown). Nine nucleic acid tests and 25 antibody tests, 12 of them point-of-care tests, had a clinical specificity of ≥ 98%. Three antibody tests achieved both thresholds. Evidence for nucleic acid point-of-care tests remains scarce at present, and sensitivity varied substantially. Study heterogeneity was low for eight of 14 sensitivity and 68 of 84 specificity results with confidence interval width ≤ 5%, and lower for nucleic acid tests than antibody tests. Manufacturer-reported clinical performance was significantly higher than independently assessed in 11 of 32 and four of 34 cases, respectively, for sensitivity and specificity, indicating a need for improvement in this area. Conclusion Continuous monitoring of clinical performance within more clearly defined target populations is needed.

Published
2021

17. Effects of Cigarette Smoke, Cessation, and Switching to Two Heat-Not-Burn Tobacco Products on Lung Lipid Metabolism in C57BL/6 and Apoe−/− Mice—An Integrative Systems Toxicology Analysis

Author

Titz, Bjoern, Boué, Stéphanie, Phillips, Blaine, Talikka, Marja, Vihervaara, Terhi, Schneider, Thomas, Nury, Catherine, Elamin, Ashraf, Guedj, Emmanuel, Peck, Michael J., Schlage, Walter K., Cabanski, Maciej, Leroy, Patrice, Vuillaume, Gregory, Martin, Florian, Ivanov, Nikolai V., Veljkovic, Emilija, Ekroos, Kim, Laaksonen, Reijo, Vanscheeuwijck, Patrick, Peitsch, Manuel C., and Hoeng, Julia

Published
2016
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23. hiPSC‐derived hepatocytes closely mimic the lipid profile of primary hepatocytes: A future personalised cell model for studying the lipid metabolism of the liver

Author

Kiamehr, Mostafa, primary, Alexanova, Anna, additional, Viiri, Leena E., additional, Heiskanen, Laura, additional, Vihervaara, Terhi, additional, Kauhanen, Dimple, additional, Ekroos, Kim, additional, Laaksonen, Reijo, additional, Käkelä, Reijo, additional, and Aalto‐Setälä, Katriina, additional

Published
2018
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24. Susceptibility of low-density lipoprotein particles to aggregate depends on particle lipidome, is modifiable, and associates with future cardiovascular deaths

Author

Ruuth, Maija, primary, Nguyen, Su Duy, additional, Vihervaara, Terhi, additional, Hilvo, Mika, additional, Laajala, Teemu D, additional, Kondadi, Pradeep Kumar, additional, Gisterå, Anton, additional, Lähteenmäki, Hanna, additional, Kittilä, Tiia, additional, Huusko, Jenni, additional, Uusitupa, Matti, additional, Schwab, Ursula, additional, Savolainen, Markku J, additional, Sinisalo, Juha, additional, Lokki, Marja-Liisa, additional, Nieminen, Markku S, additional, Jula, Antti, additional, Perola, Markus, additional, Ylä-Herttula, Seppo, additional, Rudel, Lawrence, additional, Öörni, Anssi, additional, Baumann, Marc, additional, Baruch, Amos, additional, Laaksonen, Reijo, additional, Ketelhuth, Daniel F J, additional, Aittokallio, Tero, additional, Jauhiainen, Matti, additional, Käkelä, Reijo, additional, Borén, Jan, additional, Williams, Kevin Jon, additional, Kovanen, Petri T, additional, and Öörni, Katariina, additional

Published
2018
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27. Instability of LDL particles predicts future cardiovascular deaths

Author

Ruuth, Maija, primary, Nguyen, Su Duy, additional, Vihervaara, Terhi, additional, Hilvo, Mika, additional, Laajala, Teemu Daniel, additional, Kondadi, Pradeep Kumar, additional, Anton, Gisterå, additional, Huusko, Jenni, additional, Uusitupa, Matti, additional, Schwab, Ursula, additional, Lawrence, Rudel, additional, Ketelhuth, Daniel, additional, Laaksonen, Reijo, additional, Baumann, Marc, additional, Aittokallio, Tero, additional, Jauhiainen, Matti, additional, Jan, Borén, additional, Williams, Kevin Jon, additional, Kovanen, Petri, additional, and Öörni, Katariina, additional

Published
2017
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30. hiPSC‐derived hepatocytes closely mimic the lipid profile of primary hepatocytes: A future personalised cell model for studying the lipid metabolism of the liver.

Author

Kiamehr, Mostafa, Alexanova, Anna, Viiri, Leena E., Heiskanen, Laura, Vihervaara, Terhi, Kauhanen, Dimple, Ekroos, Kim, Laaksonen, Reijo, Käkelä, Reijo, and Aalto‐Setälä, Katriina

Subjects
LIVER cells, LIPID metabolism, INDIVIDUALIZED medicine, PLURIPOTENT stem cells, CELL differentiation
Abstract

Hepatocyte‐like cells (HLCs) differentiated from human‐induced pluripotent stem cells offer an alternative platform to primary human hepatocytes (PHHs) for studying the lipid metabolism of the liver. However, despite their great potential, the lipid profile of HLCs has not yet been characterized. Here, we comprehensively studied the lipid profile and fatty acid (FA) metabolism of HLCs and compared them with the current standard hepatocyte models: HepG2 cells and PHHs. We differentiated HLCs by five commonly used methods from three cell lines and thoroughly characterized them by gene and protein expression. HLCs generated by each method were assessed for their functionality and the ability to synthesize, elongate, and desaturate FAs. In addition, lipid and FA profiles of HLCs were investigated by both mass spectrometry and gas chromatography and then compared with the profiles of PHHs and HepG2 cells. HLCs resembled PHHs by expressing hepatic markers: secreting albumin, lipoprotein particles, and urea, and demonstrating similarities in their lipid and FA profile. Unlike HepG2 cells, HLCs contained low levels of lysophospholipids similar to the content of PHHs. Furthermore, HLCs were able to efficiently use the exogenous FAs available in their medium and simultaneously modify simple lipids into more complex ones to fulfill their needs. In addition, we propose that increasing the polyunsaturated FA supply of the culture medium may positively affect the lipid profile and functionality of HLCs. In conclusion, our data showed that HLCs provide a functional and relevant model to investigate human lipid homeostasis at both molecular and cellular levels. Hepatocyte‐like cells (HLCs) offer an alternative platform to primary human hepatocytes (PHHs) for studying lipid metabolism of the liver; however, their lipid profile has not yet been characterized. We demonstrate that HLCs resemble PHHs by their functionality and showing similarities in their lipid and fatty acid (FA) profile. Unlike HepG2 cells, HLCs contained low levels of lysophospholipids, similar to the content of PHHs. Here, we propose that HLCs provide a functional and relevant model to investigate human lipid homeostasis at both molecular and cellular levels. [ABSTRACT FROM AUTHOR]

Published
2019
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31. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol

Author

University of Helsinki, Transplantation Laboratory, University of Helsinki, Medicum, University of Helsinki, Clinicum, Laaksonen, Reijo, Ekroos, Kim, Sysi-Aho, Marko, Hilvo, Mika, Vihervaara, Terhi, Kauhanen, Dimple, Suoniemi, Matti, Hurme, Reini, März, Winfried, Scharnagl, Hubert, Stojakovic, Tatjana, Vlachopoulou, Efthymia, Lokki, Marja-Liisa, Nieminen, Markku S., Klingenberg, Roland, Matter, Christian M., Hornemann, Thorsten, Jüni, Peter, Rodondi, Nicolas, Räber, Lorenz, Windecker, Stephan, Gencer, Baris, Pedersen, Eva Ringdal, Tell, Grethe S., Nygård, Ottar, Mach, Francois, Sinisalo, Juha, Lüscher, Thomas F., University of Helsinki, Transplantation Laboratory, University of Helsinki, Medicum, University of Helsinki, Clinicum, Laaksonen, Reijo, Ekroos, Kim, Sysi-Aho, Marko, Hilvo, Mika, Vihervaara, Terhi, Kauhanen, Dimple, Suoniemi, Matti, Hurme, Reini, März, Winfried, Scharnagl, Hubert, Stojakovic, Tatjana, Vlachopoulou, Efthymia, Lokki, Marja-Liisa, Nieminen, Markku S., Klingenberg, Roland, Matter, Christian M., Hornemann, Thorsten, Jüni, Peter, Rodondi, Nicolas, Räber, Lorenz, Windecker, Stephan, Gencer, Baris, Pedersen, Eva Ringdal, Tell, Grethe S., Nygård, Ottar, Mach, Francois, Sinisalo, Juha, and Lüscher, Thomas F.

Published
2016

33. Gender, Contraceptives and Individual Metabolic Predisposition Shape a Healthy Plasma Lipidome

Author

Sales, Susanne, primary, Graessler, Juergen, additional, Ciucci, Sara, additional, Al-Atrib, Rania, additional, Vihervaara, Terhi, additional, Schuhmann, Kai, additional, Kauhanen, Dimple, additional, Sysi-Aho, Marko, additional, Bornstein, Stefan R., additional, Bickle, Marc, additional, Cannistraci, Carlo V., additional, Ekroos, Kim, additional, and Shevchenko, Andrej, additional

Published
2016
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35. Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol

Author

Laaksonen, Reijo, primary, Ekroos, Kim, additional, Sysi-Aho, Marko, additional, Hilvo, Mika, additional, Vihervaara, Terhi, additional, Kauhanen, Dimple, additional, Suoniemi, Matti, additional, Hurme, Reini, additional, März, Winfried, additional, Scharnagl, Hubert, additional, Stojakovic, Tatjana, additional, Vlachopoulou, Efthymia, additional, Lokki, Marja-Liisa, additional, Nieminen, Markku S., additional, Klingenberg, Roland, additional, Matter, Christian M., additional, Hornemann, Thorsten, additional, Jüni, Peter, additional, Rodondi, Nicolas, additional, Räber, Lorenz, additional, Windecker, Stephan, additional, Gencer, Baris, additional, Pedersen, Eva Ringdal, additional, Tell, Grethe S., additional, Nygård, Ottar, additional, Mach, Francois, additional, Sinisalo, Juha, additional, and Lüscher, Thomas F., additional

Published
2016
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36. Comprehensive systems biology analysis of a 7-month cigarette smoke inhalation study in C57BL/6 mice

Author

Ansari, Sam, primary, Baumer, Karine, additional, Boué, Stéphanie, additional, Dijon, Sophie, additional, Dulize, Remi, additional, Ekroos, Kim, additional, Elamin, Ashraf, additional, Foong, Clement, additional, Guedj, Emmanuel, additional, Hoeng, Julia, additional, Ivanov, Nikolai V., additional, Krishnan, Subash, additional, Leroy, Patrice, additional, Martin, Florian, additional, Merg, Celine, additional, Peck, Michael J., additional, Peitsch, Manuel C., additional, Phillips, Blaine, additional, Schlage, Walter K., additional, Schneider, Thomas, additional, Talikka, Marja, additional, Titz, Bjoern, additional, Vanscheeuwijck, Patrick, additional, Veljkovic, Emilija, additional, Vihervaara, Terhi, additional, Vuillaume, Gregory, additional, and Woon, Ching Qing, additional

Published
2016
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37. RNA-Seq and Mass-Spectrometry-Based Lipidomics Reveal Extensive Changes of Glycerolipid Pathways in Brown Adipose Tissue in Response to Cold

Author

Marcher, Ann-Britt, Loft, Anne, Nielsen, Ronni, Vihervaara, Terhi, Madsen, Jesper Grud Skat, Sysi-Aho, Marko, Ekroos, Kim, Mandrup, Susanne, Marcher, Ann-Britt, Loft, Anne, Nielsen, Ronni, Vihervaara, Terhi, Madsen, Jesper Grud Skat, Sysi-Aho, Marko, Ekroos, Kim, and Mandrup, Susanne

Abstract

Cold exposure greatly alters brown adipose tissue (BAT) gene expression and metabolism to increase thermogenic capacity. Here, we used RNA sequencing and mass-spectrometry-based lipidomics to provide a comprehensive resource describing the molecular signature of cold adaptation at the level of the transcriptome and lipidome. We show that short-term (3-day) cold exposure leads to a robust increase in expression of several brown adipocyte genes related to thermogenesis as well as the gene encoding the hormone irisin. However, pathway analysis shows that the most significantly induced genes are those involved in glycerophospholipid synthesis and fatty acid elongation. This is accompanied by significant changes in the acyl chain composition of triacylglycerols (TAGs) as well as subspecies-selective changes of acyl chains in glycerophospholipids. These results indicate that cold adaptation of BAT is associated with significant and highly species-selective remodeling of both TAGs and glycerophospholipids.

Published
2015

39. Effects of Cigarette Smoke, Cessation, and Switching to Two Heat-Not-Burn Tobacco Products on Lung Lipid Metabolism inC57BL/6andApoe−/−Mice—An Integrative Systems Toxicology Analysis

Author

Titz, Bjoern, primary, Boué, Stéphanie, additional, Phillips, Blaine, additional, Talikka, Marja, additional, Vihervaara, Terhi, additional, Schneider, Thomas, additional, Nury, Catherine, additional, Elamin, Ashraf, additional, Guedj, Emmanuel, additional, Peck, Michael J., additional, Schlage, Walter K., additional, Cabanski, Maciej, additional, Leroy, Patrice, additional, Vuillaume, Gregory, additional, Martin, Florian, additional, Ivanov, Nikolai V., additional, Veljkovic, Emilija, additional, Ekroos, Kim, additional, Laaksonen, Reijo, additional, Vanscheeuwijck, Patrick, additional, Peitsch, Manuel C., additional, and Hoeng, Julia, additional

Published
2015
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40. Abstract 17757: Plasma Concentrations of Molecular Lipids are Associated With Coronary Plaque Characteristics and 1-Year Cardiovascular Outcome in Patients With Coronary Artery Disease

Author

Cheng, Jin M, primary, Suoniemi, Matti, additional, Kardys, Isabella, additional, Vihervaara, Terhi, additional, De Boer, Sanneke, additional, Akkerhuis, Martijn, additional, Sysi-Aho, Marko, additional, Ekroos, Kim, additional, Garcia-Garcia, Hector, additional, Oemrawsingh, Rohit, additional, Regar, Evelyn, additional, Koenig, Wolfgang, additional, Serruys, Patrick, additional, Van Geuns, Robert-Jan, additional, Boersma, Eric, additional, and Laaksonen, Reijo, additional

Published
2015
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43. The Role of Oxysterol Binding Proteins in Macrophages

Author

Helsingin yliopisto, lääketieteellinen tiedekunta, Hjelt-instituutti, Helsingfors universitet, medicinska fakulteten, Hjelt-institutet, University of Helsinki, Faculty of Medicine, Hjelt Institute, Minervan lääketieteellinen tutkimuslaitos; Terveyden ja Hyvinvoinnin laitos, Vihervaara, Terhi, Helsingin yliopisto, lääketieteellinen tiedekunta, Hjelt-instituutti, Helsingfors universitet, medicinska fakulteten, Hjelt-institutet, University of Helsinki, Faculty of Medicine, Hjelt Institute, Minervan lääketieteellinen tutkimuslaitos; Terveyden ja Hyvinvoinnin laitos, and Vihervaara, Terhi

Abstract

Biological membranes consist of several types of lipids that have important structural and functional roles. Moreover, these lipids can act as signaling molecules or affect the function of cellular proteins. Regulation of lipid homeostasis is critical for the maintenance of cellular physiology, and disturbances in lipid metabolism aspects are key components behind many diseases, including atherosclerosis. Macrophage cells play central roles in the development of atherosclerosis. The excessive uptake of modified lipoprotein particles in the vessel subendothelial space results in a proinflammatory response and the formation of macrophage foam cells. Oxysterols, oxidized cholesterol derivatives that primarily are taken up along with the modified lipoproteins, act at the crossroads of lipid metabolism and inflammation, and are important signaling lipids involved in atherogenesis. In this thesis the functions of three members of the Oxysterol Binding Protein (ORP) Family were studied in the macrophage cell type. Their role was studied by knocking down the proteins individually using lentiviruses. Moreover, the general function of these proteins was studied using other cell models. In the first part, the targeting of late endosomal protein ORP1L was investigated. ORP1L was shown to affect the motility and function of late endosomes in a sterol-dependent manner by mediating interactions between late endosomes and endoplasmic reticulum. Similar contacts between cellular compartments are also demonstrated for ORP3 and ORP8. In the second part the role of ORP8 in the macrophage was investigated by transcriptomic, biochemical and functional assays. ORP8 knockdown was shown to result in activation of several nuclear pathways and to affect cellular migration. In the third part, the lipid composition of macrophages was studied in conditions relevant for atherogenesis. The analysis revealed complex and profound changes in the cellular lipidome in the absence of ORPs, with implicat, Biologiset kalvot koostuvat erilaisista lipideistä eli rasva-aineista, joilla on tärkeitä rakenteellisia ja toiminnallisia tehtäviä. Lipiditasapainon säätely on erittäin tärkeää solujen fysiologian kannalta, ja sen häiriöt ovat keskeisessä asemassa monien tautien, kuten valtimonkovettumataudin, taustalla. ---- Makrofaagit eli syöjäsolut ovat keskeisiä soluja valtimonkovettumataudin kehittymisen kannalta, sillä ne poistavat kolesterolia valtimoiden seinämistä. Liiallisena tämä prosessi voi johtaa tulehdusreaktioon ja makrofaagien muuttumiseen vaahtosoluiksi. Kolesterolin mukana makrofaagit ottavat sisäänsä oksisteroleja, hapettuneita kolesterolijohdannaisia. Oksisterolit ovat tehokkaita signalointilipidejä, jotka säätelevät solun tulehdusreaktioita sekä rasva-aineenvaihduntaa, ja niiden määrän on havaittu kasvavan valtimonkovettumataudin edetessä. Tässä väitöskirjatyössä on tutkittu kolmen oksisteroleja sitovan proteiiniperheen (ORP) jäsenen toimintaa. ORP1L, ORP3 ja ORP8 proteiinit ilmentyvät makrofaagi-solutyypissä erityisen runsaasti. Proteiinien toimintaa tutkittiin makrofaagi-solumallissa hiljentämällä proteiineja yksi kerrallaan käyttäen hyväksi lentiviruksia. Lisäksi proteiineja tutkittiin yleisemmin käyttäen hyväksi muita solumalleja ja tekniikoita. Tutkimuksissa havaittiin, että ORP1L proteiini säätelee myöhäisten endosomien liikettä ja toimintaa solun kolesterolistatuksesta riippuvaisesti muodostamalla vuorovaikutuksen soluelinten välille. Myös ORP3- ja ORP8-proteiinien havaittiin muodostavat vastaavia vuorovaikutuksia solun eri kalvostojen välillä. ORP8:n havaittiin säätelevän eri tumankuljetusreittejä, ja vaikuttavan makrofaagien liikkuvuuteen. Kolmannessa osatyössä tutkittiin ORP-proteiinien puuttumisen vaikutusta makrofaagien lipidikoostumukseen olosuhteissa, jotka ovat olennaisia valtimonkovettumataudin kehittymisen kannalta. Proteiinien puutos aiheutti huomattavia muutoksia, mm. tulehduksellisissa lipideissä. Tulokset viittaavat siihen, että ORP-prote

Published
2012

45. Effects of Cigarette Smoke, Cessation, and Switching to Two Heat-Not-Burn Tobacco Products on Lung Lipid Metabolism in C57BL/6 and Apoe-/- Mice-An Integrative Systems Toxicology Analysis.

Author

Titz, Bjoern, Boué, Stéphanie, Phillips, Blaine, Talikka, Marja, Vihervaara, Terhi, Schneider, Thomas, Nury, Catherine, Elamin, Ashraf, Guedj, Emmanuel, Peck, Michael J., Schlage, Walter K., Cabanski, Maciej, Leroy, Patrice, Vuillaume, Gregory, Martin, Florian, Martin, Nikolai V., Veljkovic, Emilija, Kim Ekroos, Laaksonen, Reijo, and Vanscheeuwijck, Patrick

Subjects
CIGARETTE smokers -- Risk factors, CIGARETTE smokers, TOBACCO products, TOXICOLOGY, LIPID metabolism
Abstract

The impact of cigarette smoke (CS), a major cause of lung diseases, on the composition and metabolism of lung lipids is incompletely understood. Here, we integrated quantitative lipidomics and proteomics to investigate exposure effects on lung lipid metabolismin a C57BL/6 and an Apolipoprotein E-deficient (Apoe-/-) mouse study. In these studies, mice were exposed to high concentrations of 3R4F reference CS, aerosol from potential modified risk tobacco products (MRTPs) or filtered air (Sham) for up to 8 months. The 2 assessed MRTPs, the prototypical MRTP for C57BL/6 mice and the Tobacco Heating System 2.2 for Apoe-/- mice, utilize"heat-not-burn" technologies and were each matched in nicotine concentrations to the 3R4F CS. After 2 months of CS exposure, some groups were either switched to the MRTP or underwent cessation. In both mouse strains, CS strongly affected several categories of lung lipids and lipid-related proteins. Candidate surfactant lipids, surfactant proteins, and surfactant metabolizing proteins were increased. Inflammatory eicosanoids, their metabolic enzymes, and several ceramide classes were elevated. Overall, CS induced a coordinated lipid response controlled by transcription regulators such as SREBP proteins and supported by other metabolic adaptations. In contrast, most of these changes were absent in the mice exposed to the potential MRTPs, in the cessation group, and the switching group. Our findings demonstrate the complex biological response of the lungs to CS exposure and support the benefits of cessation or switching to a heat-not-burn product using a design such as those employed in this study. [ABSTRACT FROM AUTHOR]

Published
2016
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47. Lipidomic profiling of patient-specific iPSC-derived hepatocyte-like cells

Author

Kiamehr, Mostafa, Viiri, Leena E., Vihervaara, Terhi, Koistinen, Kaisa M., Hilvo, Mika, Ekroos, Kim, Käkelä, Reijo, and Aalto-Setälä, Katriina

Abstract

Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem cells (iPSCs) offer an alternative model to primary human hepatocytes to study lipid aberrations. However, the detailed lipid profile of HLCs is yet unknown. In the current study, functional HLCs were differentiated from iPSCs generated from dermal fibroblasts of three individuals by a three-step protocol through the definitive endoderm (DE) stage. In parallel, detailed lipidomic analyses as well as gene expression profiling of a set of lipid-metabolism-related genes were performed during the entire differentiation process from iPSCs to HLCs. Additionally, fatty acid (FA) composition of the cell culture media at different stages was determined. Our results show that major alterations in the molecular species of lipids occurring during DE and early hepatic differentiation stages mainly mirror the quality and quantity of the FAs supplied in culture medium at each stage. Polyunsaturated phospholipids and sphingolipids with a very long FA were produced in the cells at a later stage of differentiation. This work uncovers the previously unknown lipid composition of iPSC-HLCs and its alterations during the differentiation in conjunction with the expression of key lipid-associated genes. Together with biochemical, functional and gene expression measurements, the lipidomic analyses allowed us to improve our understanding of the concerted influence of the exogenous metabolite supply and cellular biosynthesis essential for iPSC-HLC differentiation and function. Importantly, the study describes in detail a cell model that can be applied in exploring, for example, the lipid metabolism involved in the development of fatty liver disease or atherosclerosis.

Published
2017
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