Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease

TY - JOUR

T1 - Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease

AU - Irmscher, Sarah

AU - Zipfel, Svante L H

AU - Halder, Luke D

AU - Ivanov, Lia

AU - Gonzalez-Delgado, Andres

AU - Waldeyer, Christoph

AU - Seiffert, Moritz

AU - Brunner, Fabian J

AU - von der Heide, Monika

AU - Löschmann, Ina

AU - Wulf, Sonia

AU - Czamara, Darina

AU - Papac-Milicevic, Nikolina

AU - Strauß, Olaf

AU - Lorkowski, Stefan

AU - Reichenspurner, Hermann

AU - Holers, Michael V

AU - Banda, Nirmal K

AU - Zeller, Tanja

AU - Binder, Elisabeth B

AU - Binder, Christoph J

AU - Wiech, Thorsten

AU - Zipfel, Peter F

AU - Skerka, Christine

N1 - © 2021. The Author(s).

PY - 2021/11/18

Y1 - 2021/11/18

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-021-02011-w

DO - 10.1038/s41598-021-02011-w

M3 - SCORING: Journal article

C2 - 34795372

VL - 11

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

M1 - 22511

ER -