Mona Elisabeth Skjelland

• Zamani, Mahtab; Skagen, Karolina Ryeng; Lindberg, Beate; Bjerkeli, Vigdis; Aukrust, Pål & Halvorsen, Bente [Show all 7 contributors for this article] (2024). Relationship between fibroblast growth factor in plasma and carotid plaque neovascularization: a pilot study. Frontiers in Immunology. ISSN 1664-3224. 15, p. 1–6. doi: 10.3389/fimmu.2024.1385377.
• Kong, Xiang Yi; Lauritzen, Knut Husø; Dahl, Tuva Børresdatter; Holm, Sverre; Olsen, Maria Belland & Skjelland, Mona [Show all 12 contributors for this article] (2024). CD38 deficient mice are not protected from atherosclerosis. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 705. doi: 10.1016/j.bbrc.2024.149734.
• Scutelnic, Adrian; van de Munckhof, Anita; Krzywicka, Katarzyna; van Kammen, Mayte Sánchez; Lindgren, Erik & Cordonnier, Charlotte [Show all 186 contributors for this article] (2023). Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19. European Stroke Journal. ISSN 2396-9873. 8(4), p. 1001–1010. doi: 10.1177/23969873231185213.
• Bendszus, Martin; Fiehler, Jens; Subtil, Fabien; Bonekamp, Susanne; Aamodt, Anne Hege & Fuentes, Blanca [Show all 60 contributors for this article] (2023). Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial. The Lancet. ISSN 0140-6736. 402(10414), p. 1753–1763. doi: 10.1016/S0140-6736(23)02032-9.
• Nome, Terje; Enriquez, Brian Anthony; Nome, Cecilie; Tennøe, Bjørn; Lund, Christian & Skjelland, Mona [Show all 8 contributors for this article] (2023). Clinical outcome after thrombectomy in patients with MeVO stroke: importance of clinical and technical factors. Journal of Neurology. ISSN 0340-5354. 1(2), p. 877–886. doi: 10.1007/s00415-023-12025-1. Full text in Research Archive
• Weller, Johannes; Krzywicka, Katarzyna; van de Munckhof, Anita; Dorn, Franziska; Althaus, Katharina & Bode, Felix J [Show all 43 contributors for this article] (2023). Endovascular treatment of cerebral sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia. European Stroke Journal. ISSN 2396-9873. doi: 10.1177/23969873231202363.
• Krzywicka, Katarzyna; Aguiar de Sousa, Diana; Cordonnier, Charlotte; Bode, Felix J.; Field, Thalia S. & Michalski, Dominik [Show all 52 contributors for this article] (2023). Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia. European Journal of Neurology. ISSN 1351-5101. 30(5), p. 1335–1345. doi: 10.1111/ene.15735. Full text in Research Archive
• Stø, Kristine; Skagen, Karolina Ryeng; Valeur, Jørgen; Yang, Kuan; Bjerkeli, Vigdis & Aukrust, Pål [Show all 8 contributors for this article] (2023). Increased plasma levels of non-sugar sweeteners in patients with symptomatic carotid atherosclerosis. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 57(1). doi: 10.1080/14017431.2023.2205068. Full text in Research Archive
• Enriquez, Brian Anthony; Nome, Terje; Nome, Cecilie; Tennøe, Bjørn; Lund, Christian & Beyer, Mona K. [Show all 8 contributors for this article] (2023). Predictors of outcome after endovascular treatment for tandem occlusions: a single center retrospective analysis. BMC Neurology. ISSN 1471-2377. 23, p. 1–9. doi: 10.1186/s12883-023-03127-4. Full text in Research Archive
• Seim, Bjørn Edvard; Holt, Margrethe Flesvig; Ratajska, Aleksandra; Michelsen, Annika Elisabet; Ringseth, Monica Myklebust & Halvorsen, Bente [Show all 14 contributors for this article] (2022). Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases. Frontiers in Cardiovascular Medicine. ISSN 2297-055X. 9, p. 1–9. doi: 10.3389/fcvm.2022.1073069. Full text in Research Archive
• Schultz, Nina Haagenrud; Søraas, Arne Vasli; Sørvoll, Ingvild Hausberg; Akkøk, Cigdem Ahaein; Vetlesen, Annette & Jagjit, Bhamra Singh [Show all 13 contributors for this article] (2022). Vaccine associated benign headache and cutaneous hemorrhage after ChAdOx1 nCoV-19 vaccine: A cohort study. Journal of Stroke & Cerebrovascular Diseases. ISSN 1052-3057. 32(1). doi: 10.1016/j.jstrokecerebrovasdis.2022.106860. Full text in Research Archive
• Fontaine, Margaux A. C.; Jin, Han; Gagliardi, Mick; Rousch, Mat; Wijnands, Erwin & Stoll, Monika [Show all 23 contributors for this article] (2022). Blood Milieu in Acute Myocardial Infarction Reprograms Human Macrophages for Trauma Repair. Advanced Science. ISSN 2198-3844. p. 1–14. doi: 10.1002/advs.202203053. Full text in Research Archive
• Stø, Kristine; Valeur, Jørgen; Ueland, Thor; Malmstrøm, Gunn Helen; Bjerkeli, Vigdis & Trøseid, Marius [Show all 12 contributors for this article] (2022). Fecal level of butyric acid, a microbiome-derived metabolite, is increased in patients with severe carotid atherosclerosis. Scientific Reports. ISSN 2045-2322. 12(1), p. 1–9. doi: 10.1038/s41598-022-26759-x. Full text in Research Archive
• Van De Munckhof, Anita; Lindgren, Erik; Kleinig, Timothy J.; Field, Thalia S.; Cordonnier, Charlotte & Krzywicka, Katarzyna [Show all 77 contributors for this article] (2022). Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase. Stroke. ISSN 0039-2499. 53(10), p. 3206–3210. doi: 10.1161/STROKEAHA.122.039575.
• Enriquez, Brian Anthony; Tennøe, Bjørn; Nome, Terje; Gjertsen, Øivind; Nedregaard, Bård & Sletteberg, Ruth [Show all 13 contributors for this article] (2022). Mekanisk trombektomi ved akutt hjerneinfarkt. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 142, p. 1–8. doi: 10.4045/tidsskr.21.0577. Full text in Research Archive
• Scutelnic, Adrian; Krzywicka, Katarzyna; Mbroh, Joshua; van de Munckhof, Anita; van Kammen, Mayte Sánchez & de Sousa, Diana Aguiar [Show all 105 contributors for this article] (2022). Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination. Annals of Neurology. ISSN 0364-5134. 92(4), p. 562–573. doi: 10.1002/ana.26431.
• Wiedmann, Markus; Skattør, Thor Håkon; Stray-Pedersen, Arne; Romundstad, Luis Georg; Antal, Ellen-Ann & Marthinsen, Pål Bache [Show all 16 contributors for this article] (2021). Vaccine Induced Immune Thrombotic Thrombocytopenia Causing a Severe Form of Cerebral Venous Thrombosis With High Fatality Rate: A Case Series . Frontiers in Neurology. ISSN 1664-2295. 12:721146, p. 1–7. doi: 10.3389/fneur.2021.721146. Full text in Research Archive
• Niyonzima, Nathalie; Rahman, Jubayer; Kunz, Natalie; West, Erin; Freiwald, Tilo & Desai, Jigar V. [Show all 37 contributors for this article] (2021). Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation . Science immunology. ISSN 2470-9468. 6(66), p. eabf2489–eabf2489. doi: 10.1126/sciimmunol.abf2489.
• Kong, Xiang Yi; Huse, Camilla; Yang, Kuan; Øgaard, Jonas; Jimenez, Natalia Berges & Vik, Erik Sebastian [Show all 24 contributors for this article] (2021). Endonuclease v regulates atherosclerosis through c-c motif chemokine ligand 2-mediated monocyte infiltration. Journal of the American Heart Association (JAHA). ISSN 2047-9980. 10(14). doi: 10.1161/JAHA.120.020656. Full text in Research Archive Show summary

  Background: In cardiovascular diseases, atherosclerotic disorder are the most frequent and important with respect to morbidity and mortality. Inflammation mediated by immune cells is central in all parts of the atherosclerotic progress, and further understanding of the underlying mechanisms is needed. Growing evidence suggests that deamination of adenosine‐to‐inosine in RNA is crucial for a correct immune response; nevertheless, the role of adenosine‐to‐inosine RNA editing in atherogenesis has barely been studied. Several proteins have affinity for inosines in RNA, one being ENDOV (endonuclease V), which binds and cleaves RNA at inosines. Data on ENDOV in atherosclerosis are lacking. Methods and Results: Quantitative polymerase chain reaction on ENDOV mRNA showed an increased level in human carotid atherosclerotic plaques compared with control veins. Inosine‐ribonuclease activity as measured by an enzyme activity assay is detected in immune cells relevant for the atherosclerotic process. Abolishing EndoV in atherogenic apolipoprotein E‐deficient (ApoE−/−) mice reduces the atherosclerotic plaque burden, both in size and lipid content. In addition, in a brain stroke model, mice without ENDOV suffer less damage than control mice. Finally, lack of EndoV reduces the recruitment of monocytes to atherosclerotic lesions in atherogenic ApoE−/− mice. Conclusions: ENDOV is upregulated in human atherosclerotic lesions, and data from mice suggest that ENDOV promotes atherogenesis by enhancing the monocyte recruitment into the atherosclerotic lesion, potentially by increasing the effect of CCL2 activation on these cells.

• Holm, Sverre; Kared, Hassen; Michelsen, Annika Elisabet; Kong, Xiang Yi; Dahl, Tuva Børresdatter & Schultz, Nina Haagenrud [Show all 21 contributors for this article] (2021). Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia. European Heart Journal. ISSN 0195-668X. 42(39), p. 4064–4072. doi: 10.1093/eurheartj/ehab506. Full text in Research Archive
• Grøan, Mathias; Ospel, Johanna; Ajmi, Soffien Chadli; Sandset, Else Charlotte; Kurz, Friedrich Martin Wilhelm & Skjelland, Mona [Show all 7 contributors for this article] (2021). Time-Based Decision Making for Reperfusion in Acute Ischemic Stroke. Frontiers in Neurology. ISSN 1664-2295. 12. doi: 10.3389/fneur.2021.728012. Full text in Research Archive
• Sánchez Van Kammen, Mayte; de Sousa, Diana Aguiar; Poli, Sven; Cordonnier, Charlotte; Heldner, Mirjam R. & Van De Munckhof, Anita [Show all 123 contributors for this article] (2021). Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia. JAMA Neurology. ISSN 2168-6149. doi: 10.1001/jamaneurol.2021.3619.
• Quiles Jimenez, Ana Maria Teresa; Gregersen, Ida; Sousa, Mirta; Abbas, Azhar; Kong, Xiang Yi & Alseth, Ingrun [Show all 13 contributors for this article] (2020). N6-methyladenosine in RNA of atherosclerotic plaques: An epitranscriptomic signature of human carotid atherosclerosis. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 533(4), p. 631–637. doi: 10.1016/j.bbrc.2020.09.057. Full text in Research Archive
• Niyonzima, Nathalie; Bakke, Siril Skaret; Gregersen, Ida; Holm, Sverre; Sandanger, Øystein & Orrem, Hilde Lang [Show all 22 contributors for this article] (2020). Cholesterol crystals use complement to increase NLRP3 signaling pathways in coronary and carotid atherosclerosis. EBioMedicine. ISSN 2352-3964. 60:102985, p. 1–13. doi: 10.1016/j.ebiom.2020.102985. Full text in Research Archive
• Gregersen, Ida; Michelsen, Annika; Lunde, Ngoc Nguyen; Åkerblom, Axel; Lakic, Tatevik G. & Skjelland, Mona [Show all 20 contributors for this article] (2020). Legumain in Acute Coronary Syndromes: A Substudy of the PLATO (Platelet Inhibition and Patient Outcomes) Trial. Journal of the American Heart Association (JAHA). ISSN 2047-9980. e016360. doi: 10.1161/JAHA.120.016360. Full text in Research Archive
• Lambert, Anna Tancin; Kong, Xiang Yi; Ratajczak-Tretel, Barbara; Atar, Dan; Russell, David & Skjelland, Mona Elisabet [Show all 13 contributors for this article] (2020). Biomarkers Associated with Atrial Fibrillation in Patients with Ischemic Stroke: A Pilot Study from the NOR-FIB Study. Cerebrovascular Diseases Extra. ISSN 1664-5456. 10(1), p. 11–20. doi: 10.1159/000504529. Full text in Research Archive
• Zamani, Mahtab; Skagen, Karolina Ryeng; Scott, Helge; Russell, David & Skjelland, Mona (2020). Advanced ultrasound methods in assessment of carotid plaque instability: a prospective multimodal study. BMC Neurology. ISSN 1471-2377. 20:39(1), p. 1–8. doi: 10.1186/s12883-020-1620-z. Full text in Research Archive
• Skjelland, Mona; Zamani, Mahtab; Hetlevik, Siri Opsahl; Lilleby, Vibke; Halvorsen, Bente & Skagen, Karolina Ryeng (2020). Increased endothelial activation in patients with mixed connective tissue disease. Journal of Stroke & Cerebrovascular Diseases. ISSN 1052-3057. 29:104563(2), p. 1–5. doi: 10.1016/j.jstrokecerebrovasdis.2019.104563. Full text in Research Archive
• Lunde, Ngoc Dieu Nguyen; Gregersen, Ida; Ueland, Thor; Shetelig, Christian; Holm, Sverre & Kong, Xiang Yi [Show all 31 contributors for this article] (2019). Legumain is upregulated in acute cardiovascular events and associated with improved outcome – potentially related to anti-inflammatory effects on macrophages. Atherosclerosis. ISSN 0021-9150. p. 1–9. doi: 10.1016/j.atherosclerosis.2019.12.008. Full text in Research Archive
• Zamani, Mahtab; Skagen, Karolina Ryeng; Scott, Helge; Lindberg, Beate; Russell, David & Skjelland, Mona (2019). Carotid Plaque Neovascularization Detected With Superb Microvascular Imaging Ultrasound Without Using Contrast Media. Stroke. ISSN 0039-2499. 50(11), p. 3121–3127. doi: 10.1161/STROKEAHA.119.025496. Full text in Research Archive
• Gravastrand, Caroline S.; Steinkjer, Bjørg; Halvorsen, Bente; Landsem, Anne; Skjelland, Mona & Jacobsen, Eva Astrid [Show all 12 contributors for this article] (2019). Cholesterol Crystals Induce coagulation Activation through Complement-Dependent Expression of Monocytic Tissue Factor. Journal of Immunology. ISSN 0022-1767. 203(4), p. 853–863. doi: 10.4049/jimmunol.1900503. Full text in Research Archive Show summary

  Cholesterol crystals (CC) are strong activators of complement and could potentially be involved in thromboinflammation through complement-coagulation cross-talk. To explore the coagulation-inducing potential of CC, we performed studies in lepirudin-based human whole blood and plasma models. In addition, immunohistological examinations of brain thrombi and vulnerable plaque material from patients with advanced carotid atherosclerosis were performed using polarization filter reflected light microscopy to identify CC. In whole blood, CC exposure induced a time- and concentration-dependent generation of prothrombin fragment 1+2 (PTF1.2), tissue factor (TF) mRNA synthesis, and monocyte TF expression. Blocking Abs against TF abolished CC-mediated coagulation, thus indicating involvement of the TF-dependent pathway. Blockade of FXII by corn trypsin inhibitor had a significant inhibitory effect on CC-induced PTF1.2 in platelet-free plasma, although the overall activation potential was low. CC exposure did not induce platelet aggregation, TF microparticle induction, or TF on granulocytes or eosinophils. Inhibition of complement C3 by CP40 (compstatin), C5 by eculizumab, or C5aR1 by PMX53 blocked CC-induced PTF1.2 by 90% and reduced TF+ monocytes from 18-20 to 1-2%. The physiologic relevance was supported by birefringent CC structures adjacent to monocytes (CD14), TF, and activated complement iC3b and C5b-9 in a human brain thrombus. Furthermore, monocyte influx and TF induction in close proximity to CC-rich regions with activated complement were found in a vulnerable plaque. In conclusion, CC could be active, releasable contributors to thrombosis by inducing monocyte TF secondary to complement C5aR1 signaling.

• Jusufovic, Mirza; Skagen, Karolina Ryeng; Krohg-Sørensen, Kirsten & Skjelland, Mona (2019). Current medical and surgical stroke prevention therapies for patients with carotid artery stenosis. Current Neurovascular Research. ISSN 1567-2026. 16(1), p. 96–103. doi: 10.2174/1567202616666190131162811.
• Skagen, Karolina Ryeng; Hetlevik, Siri Opsahl; Zamani, Mahtab; Lilleby, Vibke & Skjelland, Mona (2019). Preclinical Carotid Athersoclerosis in Patients With Juvenile-onset Mixed Connective Tissue Disease. Journal of Stroke & Cerebrovascular Diseases. ISSN 1052-3057. 28(5), p. 1295–1301. doi: 10.1016/j.jstrokecerebrovasdis.2019.01.027.
• Bjerknes, Silje Kristin; Toft, Mathias; Konglund, Ane; Pham, Uyen Ha Gia; Waage, Trine Rygvold & Pedersen, Lena [Show all 11 contributors for this article] (2018). Multiple microelectrode recordings in STN-DBS surgery for Parkinson's disease: a randomized study. Movement Disorders Clinical Practice. ISSN 2330-1619. 5(3), p. 296–305. doi: 10.1002/mdc3.12621. Full text in Research Archive
• Skarpengland, Tonje; Skjelland, Mona; Kong, Xiang Yi; Skagen, Karolina Ryeng; Holm, Sverre & Otterdal, Kari [Show all 16 contributors for this article] (2018). Increased levels of lectin-like oxidized low-density lipoprotein receptor-1 in ischemic stroke and transient ischemic attack. Journal of the American Heart Association (JAHA). ISSN 2047-9980. 7:e006479(2), p. 1–16. doi: 10.1161/JAHA.117.006479. Full text in Research Archive
• Johnsrud, Kjersti; Skagen, Karolina Ryeng; Seierstad, Therese; Skjelland, Mona; Russell, David & Rootwelt-Revheim, Mona-Elisabeth (2017). 18F-FDG PET/CT for the quantification of inflammation in large carotid artery plaques. Journal of Nuclear Cardiology. ISSN 1071-3581. p. 1–11. doi: 10.1007/s12350-017-1121-7.
• Gregersen, Ida; Sandanger, Øystein; Askevold, Erik Tandberg; Sagen, Ellen Lund; Yang, Kuan & Holm, Sverre [Show all 16 contributors for this article] (2017). Interleukin 27 is increased in carotid atherosclerosis and promotes NLRP3 inflammasome activation. PLOS ONE. ISSN 1932-6203. 12(11). doi: 10.1371/journal.pone.0188387. Full text in Research Archive
• Bakke, Siril Skaret; Aune, Marie Hjelmseth; Niyonzima, Nathalie; Pilely, Katrine; Ryan, Liv & Skjelland, Mona [Show all 13 contributors for this article] (2017). Cyclodextrin Reduces Cholesterol Crystal-Induced Inflammation by Modulating Complement Activation. Journal of Immunology. ISSN 0022-1767. 199(8), p. 2910–2920. doi: 10.4049/jimmunol.1700302. Full text in Research Archive Show summary

  Cholesterol crystals (CC) are abundant in atherosclerotic plaques and promote inflammatory responses via the complement system and inflammasome activation. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (BCD) is a compound that solubilizes lipophilic substances. Recently we have shown that BCD has an anti-inflammatory effect on CC via suppression of the inflammasome and liver X receptor activation. The putative effects of BCD on CC-induced complement activation remain unknown. In this study, we found that BCD bound to CC and reduced deposition of Igs, pattern recognition molecules, and complement factors on CC in human plasma. Furthermore, BCD decreased complement activation as measured by terminal complement complex and lowered the expression of complement receptors on monocytes in whole blood in response to CC exposure. In line with this, BCD also reduced reactive oxygen species formation caused by CC in whole blood. Furthermore, BCD attenuated the CC-induced proinflammatory cytokine responses (e.g., IL-1α, MIP-1α, TNF, IL-6, and IL-8) as well as regulated a range of CC-induced genes in human PBMC. BCD also regulated complement-related genes in human carotid plaques treated ex vivo. Formation of terminal complement complex on other complement-activating structures such as monosodium urate crystals and zymosan was not affected by BCD. These data demonstrate that BCD inhibits CC-induced inflammatory responses, which may be explained by BCD-mediated attenuation of complement activation. Thus, these findings support the potential for using BCD in treatment of atherosclerosis.

• Espada Serrano, Sandra; Stavik, Benedicte; Holm, Sverre; Sagen, Ellen Lund; Bjerkeli, Vigdis & Skjelland, Mona [Show all 12 contributors for this article] (2017). Tissue factor pathway inhibitor attenuates ER stress-induced inflammation in human M2-polarized macrophages. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 491(2), p. 442–448. doi: 10.1016/j.bbrc.2017.07.070. Show summary

  Endoplasmic reticulum (ER) stress has been shown to play a key role during the initiation and clinical progression of the cardiovascular diseases, such as atherosclerosis. We have recently shown that expression of tissue factor pathway inhibitor (TFPI) in human monocyte-derived macrophages (MDMs) was induced by cholesterol crystals (CC). In the present study we aimed to determine the role of TFPI under ER stress conditions using human MDMs. qRT-PCR and immunohistochemistry analysis were performed to determine the presence of the ER stress marker CCAAT/enhancer binding protein homologous protein (CHOP) and TFPI in human carotid plaque material and also in human MDMs polarized into pro-inflammatory M1 or anti-inflammatory M2 populations. CHOP mRNA levels were upregulated in the plaques compared to healthy vessels, and CHOP protein was localized in the same area as TFPI in the plaques. Both CHOP and TFPI mRNA levels were upregulated after CC treatment, especially in the M2 phenotype, and the ER stress inhibitor 4-phenylbutyric acid (PBA) reversed this effect. Furthermore, CC treatment increased the levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-8, which for TNF-α and IL-8 was inhibited by PBA, and reduced the levels of the anti-inflammatory cytokine IL-10 in M2-polarized macrophages. Knockdown of TFPI prior to CC treatment exacerbated TNF-α and IL-6 levels, but reduced IL-8 and IL-10 levels. Our results show that CC induce TFPI and cytokine expression in M2-polarized macrophages through activation of the ER stress pathway and that TFPI has a protective effect against TNF-α and IL-6 mediated inflammation. These mechanisms may have implications for the pathogenesis of atherosclerosis.

• Stavik, Benedicte; Holm, Sverre; Espada Serrano, Sandra; Iversen, Nina; Sporsheim, Bjørnar & Bjerkeli, Vigdis [Show all 12 contributors for this article] (2017). Increased expression of TFPI in human carotid stenosis. Thrombosis Research. ISSN 0049-3848. 155, p. 31–37. doi: 10.1016/j.thromres.2017.04.024. Show summary

  INTRODUCTION: Tissue factor (TF) pathway inhibitor (TFPI) is the physiological inhibitor of TF induced blood coagulation and two isoforms exists, TFPIα and TFPIβ. In atherosclerotic plaques, TFPI may inhibit TF activity and thrombus formation, which is the main cause of ischemic stroke in carotid artery disease. We aimed to identify the isoforms of TFPI present in human carotid plaques and potential sources of TFPI. MATERIALS AND METHODS: Human atherosclerotic plaques from carotid endarterectomies were used for mRNA and immunohistochemistry analyses. hPBMCs isolated from buffy coats and THP-1 cells were differentiated and polarized into M1 or M2 macrophages, and subsequently cultured with or without cholesterol crystals (CC). mRNA and protein expression were measured with qRT-PCR and ELISA, respectively, and procoagulant activity was assessed using a two-stage chromogenic assay. RESULTS: TFPIα and TFPIβ mRNA levels were significantly increased in carotid plaques, whereas TF levels were unchanged as compared to healthy arteries. Antibodies against total TFPI showed elevated levels compared to antibodies against free TFPIα, both by immunohistochemical and ELISA detection in plaques. The antibody against total TFPI also co-localized with CD68 and the M1 and M2 markers CD80 and CD163, respectively. The TFPI mRNA expression was elevated and the procoagulant activity was decreased in M2 compared to M1 polarized human macrophages. TFPI was present in early foam cell formation and CC treatment increased the TFPI mRNA expression even further in M2 macrophages. CONCLUSIONS: Our data indicate that both isoforms of TFPI are present in advanced plaques and that anti-inflammatory M2 macrophages may be a potential source of TFPI.

• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva Børresdatter; Inass, Elyouncha; Sporsheim, Bjørnar & Gregersen, Ida [Show all 12 contributors for this article] (2017). Increased levels of legumain in plasma and plaques from patients with carotid atherosclerosis. Atherosclerosis. ISSN 0021-9150. 257, p. 216–223. doi: 10.1016/j.atherosclerosis.2016.11.026. Full text in Research Archive Show summary

  Background and aims The cysteine protease legumain has been shown to be up-regulated in unstable atherosclerotic plaques. This study aims to further elucidate legumain in atherosclerosis, by examining legumain in plasma and carotid plaques from patients with carotid stenosis. Furthermore, legumain secretion from monocyte-derived macrophages treated with atherogenic lipids during macrophage polarization was studied. Methods Plasma levels of legumain from patients with carotid stenosis (n = 254), healthy controls (n = 91), and secreted from monocyte-derived macrophages were assessed by enzyme-linked-immunosorbent assay. Quantitative PCR and immunoblotting of legumain were performed on isolated plaques and legumain localization was visualized by immunohistochemistry and fluorescence microscopy. Monocyte-derived macrophages polarized to M1 or M2 macrophages were treated with VLDL, oxLDL or cholesterol crystals (CC) and the level of legumain analysed. Results Patients with carotid stenosis had significantly higher levels of plasma legumain compared with healthy controls (median 2.0 versus 1.5 ng/ml, respectively; p = 0.003), although there was no correlation between the level of legumain and the degree of stenosis, and legumain was not an independent factor to identify patients with carotid plaques. Moreover, patients with symptoms the last 2 months had higher expressions of mature legumain, cystatin C and E/M, and the macrophage markers CD80 (M1) and CD163 (M2). Legumain co-localized with both M1 and M2 macrophages within plaques, whereas legumain mRNA expression was significantly higher (p < 0.0001) in plaques compared to non-atherosclerotic arteries (controls). Furthermore, in vitro studies showed significantly increased secretion of legumain from pro-inflammatory M1 compared to pro-resolving M2 macrophages (p = 0.014), and particularly in M1 treated with CC. In plaques, legumain was localized to structures resembling foam cells. Conclusions Legumain is increased in both plasma and plaques of patients with carotid stenosis and might be a new and early biomarker of atherosclerosis.

• Varghese, Paramel G; Folkersen, Lasse; Strawbridge, Rona J.; Halvorsen, Bente; Yndestad, Arne & Ranheim, Trine [Show all 17 contributors for this article] (2016). NLRP3 inflammasome expression and activation in human atherosclerosis. Journal of the American Heart Association (JAHA). ISSN 2047-9980. 5:e003031(5), p. 1–14. doi: 10.1161/JAHA.115.003031. Full text in Research Archive
• Skagen, Karolina Ryeng; Skjelland, Mona; Zamani, Mahtab & Russell, David (2016). Unstable carotid artery plaque: New insights and controversies in diagnostics and treatment. Croatian Medical Journal. ISSN 0353-9504. 57(4), p. 311–320. doi: 10.3325/cmj.2016.57.311.
• Skagen, Karolina Ryeng; Evensen, Kristin; Scott, Helge; Krohg-Sørensen, Kirsten; Vatnehol, Svein Are & Hol, Per Kristian [Show all 8 contributors for this article] (2016). Semiautomated magnetic resonance imaging assessment of carotid plaque lipid content. Journal of Stroke & Cerebrovascular Diseases. ISSN 1052-3057. 25(8), p. 2004–2010. doi: 10.1016/j.jstrokecerebrovasdis.2016.01.043.
• Jusufovic, Mirza; Sandset, Else Charlotte; Skagen, Karolina Ryeng & Skjelland, Mona (2016). Blood pressure lowering treatment in patients with carotid artery stenosis. Current Medical Imaging. ISSN 1573-4056. 12(2), p. 148–155. doi: 10.2174/157340211202160525010133.
• Skarpengland, Tonje; Holm, Sverre; Scheffler, Katja; Gregersen, Ida; Dahl, Tuva Børresdatter & Suganthan, Rajikala [Show all 33 contributors for this article] (2016). Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice. Scientific Reports. ISSN 2045-2322. 6:28337. doi: 10.1038/srep28337. Full text in Research Archive
• Skarpengland, Tonje; Dahl, Tuva Børresdatter; Skjelland, Mona; Scheffler, Katja; Sousa, Mirta & Gregersen, Ida [Show all 20 contributors for this article] (2016). Enhanced base excision repair capacity in carotid atherosclerosis may protect nuclear DNA but not mitochondrial DNA. Free Radical Biology & Medicine. ISSN 0891-5849. 97, p. 386–397. doi: 10.1016/j.freeradbiomed.2016.07.001.
• Zimmer, Sebastian; Grebe, Alena; Bakke, Siril Skaret; Bode, Niklas; Halvorsen, Bente & Ulas, Thomas [Show all 25 contributors for this article] (2016). Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Science Translational Medicine. ISSN 1946-6234. 8(333). doi: 10.1126/scitranslmed.aad6100. Full text in Research Archive
• Skagen, Karolina Ryeng; Trøseid, Marius; Ueland, Thor; Holm, Sverre; Abbas, Azhar & Gregersen, Ida [Show all 17 contributors for this article] (2016). The Carnitine-butyrobetaine-trimethylamine-N-oxide pathway and its association with cardiovascular mortality in patients with carotid atherosclerosis. Atherosclerosis. ISSN 0021-9150. 247, p. 64–69. doi: 10.1016/j.atherosclerosis.2016.01.033.
• Abbas, Azhar; Gregersen, Ida; Holm, Sverre; Daissormont, Isabelle; Bjerkeli, Vigdis & Krohg-Sørensen, Kirsten [Show all 19 contributors for this article] (2015). Interleukin 23 levels are increased in carotid atherosclerosis: Possible role for the interleukin 23/interleukin 17 axis. Stroke. ISSN 0039-2499. 46(3), p. 793–799. doi: 10.1161/STROKEAHA.114.006516.
• Halvorsen, Bente; Espeland, Martine Z.; Andersen, Geir Øystein; Yndestad, Arne; Sagen, Ellen Lund & Rashidi, Azita [Show all 16 contributors for this article] (2015). Increased expression of NAMPT in PBMC from patients with acute coronary syndrome and in inflammatory M1 macrophages. Atherosclerosis. ISSN 0021-9150. 243(1), p. 204–210. doi: 10.1016/j.atherosclerosis.2015.09.010.
• Skagen, Karolina Ryeng; Johnsrud, Kjersti; Evensen, Kristin; Scott, Helge; Krohg-Sørensen, Kirsten & Reier-Nilsen, Frode [Show all 10 contributors for this article] (2015). Carotid plaque inflammation assessed with 18F-FDG PET/CT is higher in symptomatic compared with asymptomatic patients. International Journal of Stroke. ISSN 1747-4930. 10(5), p. 730–736. doi: 10.1111/ijs.12430.
• Skagen, Karolina Ryeng; Skjelland, Mona; Russell, David & Jacobsen, Eva Astrid (2015). Large-vessel occlusion stroke: Effect of recanalization on outcome depends on the National Institutes of Health Stroke scale score. Journal of Stroke & Cerebrovascular Diseases. ISSN 1052-3057. 24(7), p. 1532–1539. doi: 10.1016/j.jstrokecerebrovasdis.2015.03.020.
• Bot, Ilze; Daissormont, Isabelle T.M.N.; Zernecke, Alma; van Puijvelde, Gijs H.M.; Kramp, Birgit & de Jager, Saskia C.A. [Show all 22 contributors for this article] (2014). CXCR4 blockade induces atherosclerosis by affecting neutrophil function. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 74, p. 44–52. doi: 10.1016/j.yjmcc.2014.04.021.
• Halvorsen, Bente ; Dahl, Tuva Børresdatter; Smedbakken, Linda Merete; Singh, Anjana; Michelsen, Annika & Skjelland, Mona [Show all 15 contributors for this article] (2014). Increased levels of CCR7 ligands in carotid atherosclerosis: Different effects in macrophages and smooth muscle cells. Cardiovascular Research (CVR). ISSN 0008-6363. 102(1), p. 148–156. doi: 10.1093/cvr/cvu036.
• Børretzen, Mari Naumann; Bjerknes, Silje Kristin; Sæhle, Terje; Skjelland, Mona; Skogseid, Inger Marie & Toft, Mathias [Show all 7 contributors for this article] (2014). Long-term follow-up of thalamic deep brain stimulation for essential tremor - patient satisfaction and mortality. BMC Neurology. ISSN 1471-2377. 14(120). doi: 10.1186/1471-2377-14-120.
• Halvorsen, Bente ; Smedbakken, Linda Merete; Michelsen, Annika ; Skjelland, Mona; Bjerkeli, Vigdis & Sagen, Ellen Lund [Show all 12 contributors for this article] (2014). Activated platelets promote increased monocyte expression of CXCR5 through prostaglandin E2-related mechanisms and enhance the anti-inflammatory effects of CXCL13. Atherosclerosis. ISSN 0021-9150. 234(2), p. 352–359. doi: 10.1016/j.atherosclerosis.2014.03.021.
• Abbas, Azhar; Aukrust, Pål; Russell, David; Krohg-Sørensen, Kirsten; Almås, Trine & Bundgaard, Dorte [Show all 14 contributors for this article] (2014). Matrix metalloproteinase 7 is associated with symptomatic lesions and adverse events in patients with carotid atherosclerosis. PLOS ONE. ISSN 1932-6203. 9(1:e84935). doi: 10.1371/journal.pone.0084935.
• Jusufovic, Mirza; Thomassen, Lars & Skjelland, Mona (2014). Hjerneinfarkt ved åpent foramen ovale. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 134(2), p. 180–184. doi: 10.4045/tidsskr.13.0038.
• Gregersen, Ida; Skjelland, Mona; Holm, Sverre; Holven, Kirsten Bjørklund; Sørensen, Kirsten & Russell, David [Show all 14 contributors for this article] (2013). Increased Systemic and Local Interleukin 9 Levels in Patients with Carotid and Coronary Atherosclerosis. PLOS ONE. ISSN 1932-6203. 8(8). doi: 10.1371/journal.pone.0072769. Full text in Research Archive
• Smedbakken, Linda Merete; Halvorsen, Bente ; Daissormont, Isabelle; Ranheim, Trine; Michelsen, Annika & Skjelland, Mona [Show all 19 contributors for this article] (2012). Increased levels of the homeostatic chemokine CXCL13 in human atherosclerosis - Potential role in plaque stabilization. Atherosclerosis. ISSN 0021-9150. 224(1), p. 266–273. doi: 10.1016/j.atherosclerosis.2012.06.071.
• Abbas, Azhar; Aukrust, Pål; Dahl, Tuva Børresdatter; Bjerkeli, Vigdis; Sagen, Ellen Lund & Michelsen, Annika [Show all 11 contributors for this article] (2012). High Levels of S100A12 Are Associated With Recent Plaque Symptomatology in Patients With Carotid Atherosclerosis. Stroke. ISSN 0039-2499. 43(5), p. 1347–1353. doi: 10.1161/STROKEAHA.111.642256.
• Holm, Sverre; Ueland, Thor; Dahl, Tuva Børresdatter; Michelsen, Annika ; Skjelland, Mona & Russell, David [Show all 14 contributors for this article] (2011). Fatty Acid Binding Protein 4 Is Associated with Carotid Atherosclerosis and Outcome in Patients with Acute Ischemic Stroke. PLOS ONE. ISSN 1932-6203. 6(12). doi: 10.1371/journal.pone.0028785. Show summary

  Background and Purpose: Fatty acid binding protein 4 (FABP4) has been shown to play an important role in macrophage cholesterol trafficking and associated inflammation. To further elucidate the role of FABP4 in atherogenesis in humans, we examined the regulation of FABP4 in carotid atherosclerosis and ischemic stroke. Methods: We examined plasma FABP4 levels in asymptomatic (n = 28) and symptomatic (n = 31) patients with carotid atherosclerosis, as well as in 202 subjects with acute ischemic stroke. In a subgroup of patients we also analysed the expression of FABP4 within the atherosclerotic lesion. In addition, we investigated the ability of different stimuli with relevance to atherosclerosis to regulate FABP4 expression in monocytes/macrophages. Results: FABP4 levels were higher in patients with carotid atherosclerosis, both systemically and within the atherosclerotic lesion, with particular high mRNA levels in carotid plaques from patients with the most recent symptoms. Immunostaining of carotid plaques localized FABP4 to macrophages, while activated platelets and oxidized LDL were potent stimuli for FABP4 expression in monocytes/macrophages in vitro. When measured at the time of acute ischemic stroke, high plasma levels of FABP4 were significantly associated with total and cardiovascular mortality during follow-up, although we did not find that addition of FABP4 to the fully adjusted multivariate model had an effect on the prognostic discrimination for allcause mortality as assessed by c-statistics. Conclusions: FABP4 is linked to atherogenesis, plaque instability and adverse outcome in patients with carotid atherosclerosis and acute ischemic stroke.

• Toft, Mathias; Lilleeng, Bård; Ramm-Pettersen, Jon-Terje; Skogseid, Inger Marie; Gundersen, Vidar & Gerdts, Reno [Show all 10 contributors for this article] (2011). Long-Term Efficacy and Mortality in Parkinson's Disease Patients Treated with Subthalamic Stimulation. Movement Disorders. ISSN 0885-3185. 26(10), p. 1931–1934. doi: 10.1002/mds.23817.
• Aukrust, Pål; Halvorsen, Bente ; Ueland, Thor; Michelsen, Annika ; Skjelland, Mona & Gullestad, Lars [Show all 8 contributors for this article] (2010). Activated platelets and atherosclerosis. Expert Review of Cardiovascular Therapy. ISSN 1477-9072. 8(9), p. 1297–1307. doi: 10.1586/erc.10.92.
• Michelsen, Annika ; Rathcke, CN; Skjelland, Mona; Holm, Sverre; Ranheim, Trine & Krohg-Sørensen, Kirsten [Show all 12 contributors for this article] (2010). Increased YKL-40 expression in patients with carotid atherosclerosis. Atherosclerosis. ISSN 0021-9150. 211(2), p. 589–595. doi: 10.1016/j.atherosclerosis.2010.02.035.
• Breland, Unni Mathilde; Michelsen, Annika ; Skjelland, Mona; Folkersen, L; Krohg-Sørensen, Kirsten & Russell, David [Show all 14 contributors for this article] (2010). Raised MCP-4 levels in symptomatic carotid atherosclerosis: an inflammatory link between platelet and monocyte activation. Cardiovascular Research (CVR). ISSN 0008-6363. 86(2), p. 265–273. doi: 10.1093/cvr/cvq044.
• Ederle, Jörg; Dobson, J; Featherstone, RL; Bonati, LH; van der Worp, HB & de Borst, GJ [Show all 347 contributors for this article] (2010). Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. The Lancet. ISSN 0140-6736. 375(9719), p. 985–997. doi: 10.1016/S0140-6736(10)60239-5.
• Krohg-Sørensen, Kirsten; Lingaas, Per Snorre; Bakke, Jacob & Skjelland, Mona (2009). Åpen kirurgi og endovaskulær behandling av carotisstenose. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 129(21), p. 2244–2247.
• Skjelland, Mona; Krohg-Sørensen, Kirsten; Tennøe, Bjørn; Bakke, Søren; Brucher, Rainer & Russell, David (2009). Cerebral Microemboli and Brain Injury During Carotid Artery Endarterectomy and Stenting. Stroke. ISSN 0039-2499. 40(1), p. 230–234. doi: 10.1161/STROKEAHA.107.513341.
• Halvorsen, Bente ; Otterdal, K; Dahl, TB; Skjelland, Mona; Gullestad, Lars & Øie, Erik [Show all 7 contributors for this article] (2008). Atherosclerotic Plaque Stability-What Determines the Fate of a Plaque? Progress in cardiovascular diseases. ISSN 0033-0620. 51(3), p. 183–194. doi: 10.1016/j.pcad.2008.09.001.
• Handberg, Aase; Skjelland, Mona; Michelsen, Annika ; Sagen, Ellen Lund; Krohg-Sørensen, Kirsten & Russell, David [Show all 11 contributors for this article] (2008). Soluble CD36 in plasma is increased in patients with symptomatic atherosclerotic carotid plaques and is related to plaque instability. Stroke. ISSN 0039-2499. 39, p. 3092–3095. doi: 10.1161/STROKEAHA.108.517128.
• Skjelland, Mona; Michelsen, Annika ; Brosstad, Frank Roger; Svennevig, Jan Ludvig; Brucher, R & Russell, David (2008). Solid cerebral microemboli and cerebrovascular symptoms in patients with prosthetic heart valves. Stroke. ISSN 0039-2499. 39. doi: 10.1161/STROKEAHA.107.493031.
• Dahl, Tuva Børresdatter; Yndestad, Arne; Skjelland, Mona; Øie, Erik; Dahl, Arve & Michelsen, Annika [Show all 18 contributors for this article] (2007). Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization. Circulation. ISSN 0009-7322. 115, p. 972–980. doi: 10.1161/CIRCULATIONAHA.106.665893.
• Skjelland, Mona; Michelsen, Annika ; Krogh-Sørensen, K; Tennøe, Bjørn; Dahl, Arve & Bakke, Jacob [Show all 11 contributors for this article] (2007). Plasma levels of granzyme B are increased in patients with lipid-rich carotid plaques as determined by echogenicity. Atherosclerosis. ISSN 0021-9150. 195, p. e142–e146.

View all works in Cristin

• Stavik, Benedicte; Andresen, Marianne Seierstad; Holm, Sverre; Skjelland, Mona; Tinholt, Mari & Sandset, Per Morten [Show all 8 contributors for this article] (2021). Increased levels of coagulation factor V in atherosclerotic plaques - an immune regulated response? . Research and Practice in Thrombosis and Haemostasis (RPTH). ISSN 2475-0379. 5.
• Stø, Kristine; Valeur, Jørgen; Ueland, Thor; Malmstrøm, Gunn Helen; Bjerkeli, Vigdis & Kazmi, Syed Sajid Hussain [Show all 10 contributors for this article] (2021). Increased fecal levels of the SCFA butyrate may indicate poor absorption due to disrupted gut barrier in patients with carotid stenosis.
• Zamani, Mahtab; Skagen, Karolina Ryeng; Russell, David & Skjelland, Mona (2020). Response by Zamani et al to Letter Regarding Article, "Carotid Plaque Neovascularization Detected With Superb Microvascular Imaging Ultrasound Without Using Contrast Media". Stroke. ISSN 0039-2499. 51(1). doi: 10.1161/STROKEAHA.119.027944.
• Skagen, Karolina; Aamodt, Anne Hege; Enriquez, Brian & Skjelland, Mona Elisabet (2020). For lite kunnskap om blodtrykk ved hjerneinfarkt. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 140(9), p. 1–3. doi: 10.4045/tidsskr.20.0323.
• Skjelland, Mona & Mathiesen, Ellisiv B. (2019). Ultralydundersøkelse av precerebrale og intracerebrale arterier, Nevrologi og nevrokirurgi. Fra barn til voksen, 7. utg. . Fagbokforlaget. ISSN 978-82-450-2473-9. p. 125–131.
• Gravastrand, Caroline S.; Steinkjer, Bjørg; Halvorsen, Bente; Landsem, Anne; Skjelland, Mona & Jacobsen, Eva Astrid [Show all 12 contributors for this article] (2019). Cholesterol crystals induce thromboinflammation.
• Rokstad, Anne Mari; Gravastrand, Caroline S.; Halvorsen, Bente; Steinkjer, Bjørg; Skjelland, Mona & Jacobsen, Eva Astrid [Show all 10 contributors for this article] (2018). Cholesterol crystals induce coagulation that can be prevented by targeting complement.
• Stavik, Benedicte; Tinholt, Mari; Skjelland, Mona; Espevik, Terje; Sandset, Per Morten & Halvorsen, Bente [Show all 7 contributors for this article] (2018). Coagulation factors in human atherosclerotic plaques – a potential link to inflammation?
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva Børresdatter; Elyouncha, Inass; Sporsheim, Bjørnar & Gregersen, Ida [Show all 12 contributors for this article] (2018). Plasma and plaques from patients with carotid atherosclerosis have increased levels of legumain .
• Stavik, Benedicte; Espada, Sandra; Holm, Sverre; Bjerkeli, Vigdis; Sandset, Per Morten & Dahl, Tuva Børresdatter [Show all 11 contributors for this article] (2017). TFPI in human atherosclerotic plaques. Research and Practice in Thrombosis and Haemostasis (RPTH). ISSN 2475-0379. 1(s1).
• Lunde, Ngoc Nguyen Dieu; Holm, Sverre; Dahl, Tuva B.; Elyoncha, Inass; Sporsheim, Bjørnar & Gregersen, Ida [Show all 12 contributors for this article] (2017). Plasma and plaques from patients with carotid atherosclerosis have increased levels of legumain.
• Bakke, Siril Skaret; Aune, Marie Hjelmseth; Niyonzima, Nathalie; Pilely, Katrine; Ryan, Liv & Skjelland, Mona [Show all 13 contributors for this article] (2017). Cyclodextrin inhibits CC-induced complement activation.
• Espevik, Terje; Niyonzima, Nathalie; Bakke, Siril Skaret; Halvorsen, Bente; Gregersen, Ida & Skjelland, Mona [Show all 13 contributors for this article] (2017). Systemic- and local complement activation controls the NLRP3 inflammasome pathway in patients with atherosclerosis.
• Stavik, Benedicte; Holm, Sverre; Espada, Sandra; Iversen, Nina; Sporsheim, Bjørnar & Bjerkeli, Vigdis [Show all 12 contributors for this article] (2016). Unconventional mechanisms of targeting atherosclerosis.
• Stavik, Benedicte; Espada, Sandra; Holm, Sverre; Bjerkeli, Vigdis; Sandset, Per Morten & Dahl, Tuva Børresdatter [Show all 11 contributors for this article] (2016). Cholesterol crystals induce TFPI expression in alternatively activated human monocyte-derived macrophages. Show summary

  Atherosclerotic disease is denoted by low density lipoprotein (LDL) influx and retention in the artery intima, triggering the recruitment of monocytes causing a low grade chronic inflammation. Tissue factor (TF) pathway inhibitor (TFPI) regulates TF induced blood coagulation. Two isoforms exist, TFPIα and TFPIβ. In addition, TFPIα is also found complexed with LDL with unknown function. Moreover, ApoE-/- TFPI-/+ double KO mice display an atherogenic phenotype. We aimed to identify the cells expressing TFPI isoforms in human atherosclerotic plaques and the function of TFPI in these cells.

• Espada Serrano, Sandra; Holm, Sverre; Bjerkeli, Vigdis; Skjelland, Mona; Dahl, Tuva Børresdatter & Iversen, Nina [Show all 11 contributors for this article] (2016). ER stress conditions lead to an upregulation of TFPI and is associated with an anti-apoptotic macrophage phenotype. Show summary

  Endoplasmic reticulum (ER) stress is an important event during the initiation and clinical progression of several cardiovascular diseases, including atherosclerosis. In the present study we determined the role of tissue factor pathway inhibitor (TFPI) under ER stress conditions using human monocyte-derived macrophages (PBMC) and human carotid endarterectomies. TFPI was expressed in carotid plaques from patients with internal carotid stenosis, especially the TFPIα isoform. Moreover, TFPI colocalized with the ER stress marker CHOP in the plaques. Cholesterol crystals (CC) were used in human M1 and M2-polarized macrophages in vitro as an inducer of ER stress. CHOP and TFPI mRNA levels were upregulated after CC treatment, especially in the M2 phenotype. The ER stress inhibitor 4-Phenylbutyric acid (PBA) reversed the CC-mediated upregulation of CHOP and TFPI. Furthermore, M2-polarized macrophages incubated with CC had higher levels of Bcl-2:Bax mRNA ratios and Bcl-2 protein expression, and these effects were reversed by TFPI knockdown and PBA treatment. Our results indicate that TFPI could promote survival of the M2-polarized macrophages under ER stress conditions. These findings may have implications for the pathogenesis of atherosclerosis.

• Zamani, Mathab; Skagen, Karolina Ryeng; Skjelland, Mona & Russell, David (2015). The assessment of neovscularization in carotid artery plaques and ischemic stroke using Superb Microvascular Imaging. International Journal of Stroke. ISSN 1747-4930. 10, p. 1–458.
• Skagen, Karolina Ryeng; Evensen, Kristin; Scott, Helge; Krohg-Sørensen, Kirsten; Vatnehol, Svein Are & Hol, Per Kristian [Show all 8 contributors for this article] (2015). Carotid plaque lipid content on MRI is associated with plaque instability. Cerebrovascular Diseases. ISSN 1015-9770.
• Skagen, Karolina Ryeng; Skjelland, Mona; Scott, Helge; Hol, Per Kristian & Russell, David (2015). Assessment of the unstable carotid artery plaque using 3T MRI. International Journal of Stroke. ISSN 1747-4930. 10, p. 1–458.
• Skagen, Karolina Ryeng; Marthinsen, Pål Bache; Skjelland, Mona & Russell, David (2015). Fluktuerende carotistumor . Tidsskrift for Den norske legeforening. ISSN 0029-2001. 134(4).
• Jusufovic, Mirza; Konglund, Ane; Beyer, Mona K.; Dietrichs, Espen & Skjelland, Mona (2014). Deep brain stimulation in essential tremor. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 134, p. 1757–1757.
• Skagen, Karolina Ryeng; Skjelland, Mona; Russell, David & Jacobsen, Eva Astrid (2013). Large vessel occlusion stroke: effect of recanalization on outcome depends on NIHSS score. Cerebrovascular Diseases. ISSN 1015-9770. 35, p. 178–178.
• Skagen, Karolina Ryeng; Skjelland, Mona; Russell, David & Jacobsen, Eva Astrid (2013). Natural history of large vessel occlusion stroke. Cerebrovascular Diseases. ISSN 1015-9770. 35, p. 340–340.
• Skagen, Karolina Ryeng; Skjelland, Mona; Scott, Helge; Hol, Per Kristian & Russell, David (2013). Assessment of the unstable carotid plaque using 3T MRI. Cerebrovascular Diseases. ISSN 1015-9770. 35, p. 48–48.
• Skjelland, Mona & Russell, David (2008). Cerebral microemboli, atherosclerosis and ischemic brain injury. Unipub forlag. ISSN 978-82-8072-758-9.

View all works in Cristin