Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease
| Autor: | Irmscher, Sarah, Zipfel, Svante L. H., Halder, Luke D., Ivanov, Lia, Gonzalez-Delgado, Andres, Waldeyer, Christoph, Seiffert, Moritz, Brunner, Fabian J., von der Heide, Monika, Löschmann, Ina, Wulf, Sonia, Czamara, Darina, Papac-Milicevic, Nikolina, Strauß, Olaf, Lorkowski, Stefan, Reichenspurner, Hermann, Holers, Michael V., Banda, Nirmal K., Zeller, Tania, Binder, Elisabeth B., Binder, Christoph J., Wiech, Thorsten, Zipfel, Peter F., Skerka, Christine |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Molecular biology Science Immunology Cardiology Diseases Pathogenesis Article Necrosis Medical research Genetics Complement C3b Inactivator Proteins Humans Complement Activation Aged Sequence Deletion Inflammation Molecular medicine Gene Expression Profiling Homozygote Middle Aged Atherosclerosis Lipids Oxygen Gene Expression Regulation Cardiovascular Diseases embryonic structures Medicine Female Chromosome Deletion |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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