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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f4fef222f3624b56b6f873bb7fc7bb7a
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spelling	oai:doaj.org-article:f4fef222f3624b56b6f873bb7fc7bb7a2021-11-21T12:20:23ZFactor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease10.1038/s41598-021-02011-w2045-2322https://doaj.org/article/f4fef222f3624b56b6f873bb7fc7bb7a2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02011-whttps://doaj.org/toc/2045-2322Abstract 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.Sarah IrmscherSvante L. H. ZipfelLuke D. HalderLia IvanovAndres Gonzalez-DelgadoChristoph WaldeyerMoritz SeiffertFabian J. BrunnerMonika von der HeideIna LöschmannSonia WulfDarina CzamaraNikolina Papac-MilicevicOlaf StraußStefan LorkowskiHermann ReichenspurnerMichael V. HolersNirmal K. BandaTania ZellerElisabeth B. BinderChristoph J. BinderThorsten WiechPeter F. ZipfelChristine SkerkaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	factor h-related protein 1 (fhr-1) is associated with atherosclerotic cardiovascular disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f4fef222f3624b56b6f873bb7fc7bb7a
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Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease

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