Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease
Abstract Atherosclerotic cardiovascular disease (ACVD) is a lipid-driven inflammatory disease and one of the leading causes of death worldwide. Lipid deposits in the arterial wall lead to the formation of plaques that involve lipid oxidation, cellular necrosis, and complement activation, resulting i...
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| Format: | Article |
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Nature Portfolio
2021-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-02011-w |
| _version_ | 1819004529324064768 |
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| author | Sarah Irmscher Svante L. H. Zipfel Luke D. Halder Lia Ivanov Andres Gonzalez-Delgado Christoph Waldeyer Moritz Seiffert Fabian J. Brunner Monika von der Heide Ina Löschmann Sonia Wulf Darina Czamara Nikolina Papac-Milicevic Olaf Strauß Stefan Lorkowski Hermann Reichenspurner Michael V. Holers Nirmal K. Banda Tania Zeller Elisabeth B. Binder Christoph J. Binder Thorsten Wiech Peter F. Zipfel Christine Skerka |
| author_facet | Sarah Irmscher Svante L. H. Zipfel Luke D. Halder Lia Ivanov Andres Gonzalez-Delgado Christoph Waldeyer Moritz Seiffert Fabian J. Brunner Monika von der Heide Ina Löschmann Sonia Wulf Darina Czamara Nikolina Papac-Milicevic Olaf Strauß Stefan Lorkowski Hermann Reichenspurner Michael V. Holers Nirmal K. Banda Tania Zeller Elisabeth B. Binder Christoph J. Binder Thorsten Wiech Peter F. Zipfel Christine Skerka |
| author_sort | Sarah Irmscher |
| collection | DOAJ |
| description | Abstract Atherosclerotic cardiovascular disease (ACVD) is a lipid-driven inflammatory disease and one of the leading causes of death worldwide. Lipid deposits in the arterial wall lead to the formation of plaques that involve lipid oxidation, cellular necrosis, and complement activation, resulting in inflammation and thrombosis. The present study found that homozygous deletion of the CFHR1 gene, which encodes the plasma complement protein factor H-related protein 1 (FHR-1), was protective in two cohorts of patients with ACVD, suggesting that FHR-1 accelerates inflammation and exacerbates the disease. To test this hypothesis, FHR-1 was isolated from human plasma and was found to circulate on extracellular vesicles and to be deposited in atherosclerotic plaques. Surface-bound FHR-1 induced the expression of pro-inflammatory cytokines and tissue factor in both monocytes and neutrophils. Notably, plasma concentrations of FHR-1, but not of factor H, were significantly (p < 0.001) elevated in patients with ACVD, and correlated with the expression of the inflammation markers C-reactive protein, apolipoprotein serum amyloid protein A, and neopterin. FHR-1 expression also significantly correlated with plasma concentrations of low-density lipoprotein (LDL) (p < 0.0001) but not high-density lipoprotein (HDL). Taken together, these findings suggest that FHR-1 is associated with ACVD. |
| first_indexed | 2024-12-20T23:38:21Z |
| format | Article |
| id | doaj.art-f4fef222f3624b56b6f873bb7fc7bb7a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T23:38:21Z |
| publishDate | 2021-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f4fef222f3624b56b6f873bb7fc7bb7a2022-12-21T19:23:09ZengNature PortfolioScientific Reports2045-23222021-11-0111111510.1038/s41598-021-02011-wFactor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular diseaseSarah Irmscher0Svante L. H. Zipfel1Luke D. Halder2Lia Ivanov3Andres Gonzalez-Delgado4Christoph Waldeyer5Moritz Seiffert6Fabian J. Brunner7Monika von der Heide8Ina Löschmann9Sonia Wulf10Darina Czamara11Nikolina Papac-Milicevic12Olaf Strauß13Stefan Lorkowski14Hermann Reichenspurner15Michael V. Holers16Nirmal K. Banda17Tania Zeller18Elisabeth B. Binder19Christoph J. Binder20Thorsten Wiech21Peter F. Zipfel22Christine Skerka23Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection BiologyClinic for Heart and Visceral Surgery, University Heart and Vascular Center Hamburg, Medical University Hamburg-EppendorfDepartment of Infection Biology, Leibniz Institute for Natural Product Research and Infection BiologyDepartment of Infection Biology, Leibniz Institute for Natural Product Research and Infection BiologyDepartment of Infection Biology, Leibniz Institute for Natural Product Research and Infection BiologyDepartment of General and Interventional Cardiology, University Heart and Vascular Center Hamburg, Medical University Hamburg-EppendorfDepartment of General and Interventional Cardiology, University Heart and Vascular Center Hamburg, Medical University Hamburg-EppendorfDepartment of General and Interventional Cardiology, University Heart and Vascular Center Hamburg, Medical University Hamburg-EppendorfDepartment of Infection Biology, Leibniz Institute for Natural Product Research and Infection BiologyDepartment of Infection Biology, Leibniz Institute for Natural Product Research and Infection BiologyInstitute of Pathology, Medical University Hamburg-EppendorfDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Laboratory Medicine, Medical University of ViennaDepartment of Ophthalmology, Charité –University Medicine Berlin, a Corporate Member of Free University, Humboldt-University and the Berlin Institute of HealthInstitute for Nutritional Sciences, Friedrich Schiller UniversityClinic for Heart and Visceral Surgery, University Heart and Vascular Center Hamburg, Medical University Hamburg-EppendorfDivision of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical CampusDivision of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical CampusDepartment of General and Interventional Cardiology, University Heart and Vascular Center Hamburg, Medical University Hamburg-EppendorfDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Laboratory Medicine, Medical University of ViennaInstitute of Pathology, Medical University Hamburg-EppendorfDepartment of Infection Biology, Leibniz Institute for Natural Product Research and Infection BiologyDepartment of Infection Biology, Leibniz Institute for Natural Product Research and Infection BiologyAbstract Atherosclerotic cardiovascular disease (ACVD) is a lipid-driven inflammatory disease and one of the leading causes of death worldwide. Lipid deposits in the arterial wall lead to the formation of plaques that involve lipid oxidation, cellular necrosis, and complement activation, resulting in inflammation and thrombosis. The present study found that homozygous deletion of the CFHR1 gene, which encodes the plasma complement protein factor H-related protein 1 (FHR-1), was protective in two cohorts of patients with ACVD, suggesting that FHR-1 accelerates inflammation and exacerbates the disease. To test this hypothesis, FHR-1 was isolated from human plasma and was found to circulate on extracellular vesicles and to be deposited in atherosclerotic plaques. Surface-bound FHR-1 induced the expression of pro-inflammatory cytokines and tissue factor in both monocytes and neutrophils. Notably, plasma concentrations of FHR-1, but not of factor H, were significantly (p < 0.001) elevated in patients with ACVD, and correlated with the expression of the inflammation markers C-reactive protein, apolipoprotein serum amyloid protein A, and neopterin. FHR-1 expression also significantly correlated with plasma concentrations of low-density lipoprotein (LDL) (p < 0.0001) but not high-density lipoprotein (HDL). Taken together, these findings suggest that FHR-1 is associated with ACVD.https://doi.org/10.1038/s41598-021-02011-w |
| spellingShingle | Sarah Irmscher Svante L. H. Zipfel Luke D. Halder Lia Ivanov Andres Gonzalez-Delgado Christoph Waldeyer Moritz Seiffert Fabian J. Brunner Monika von der Heide Ina Löschmann Sonia Wulf Darina Czamara Nikolina Papac-Milicevic Olaf Strauß Stefan Lorkowski Hermann Reichenspurner Michael V. Holers Nirmal K. Banda Tania Zeller Elisabeth B. Binder Christoph J. Binder Thorsten Wiech Peter F. Zipfel Christine Skerka Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease Scientific Reports |
| title | Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease |
| title_full | Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease |
| title_fullStr | Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease |
| title_full_unstemmed | Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease |
| title_short | Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease |
| title_sort | factor h related protein 1 fhr 1 is associated with atherosclerotic cardiovascular disease |
| url | https://doi.org/10.1038/s41598-021-02011-w |
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