It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
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.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 Leibniz Institute for Natural Product Research and Infection Biology, Department of Infection Biology, Jena, Germany (GRID:grid.418398.f) (ISNI:0000 0001 0143 807X); Hannover Medical School, Institute of Cell Biochemistry, Hannover, Germany (GRID:grid.10423.34) (ISNI:0000 0000 9529 9877)
2 Medical University Hamburg-Eppendorf, Clinic for Heart and Visceral Surgery, University Heart and Vascular Center Hamburg, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484)
3 Leibniz Institute for Natural Product Research and Infection Biology, Department of Infection Biology, Jena, Germany (GRID:grid.418398.f) (ISNI:0000 0001 0143 807X)
4 Medical University Hamburg-Eppendorf, Department of General and Interventional Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484); German Center for Cardiovascular Research (DZHK) Partner Site Hamburg/Lübeck/Kiel, Hamburg, Germany (GRID:grid.13648.38)
5 Medical University Hamburg-Eppendorf, Department of General and Interventional Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484)
6 Medical University Hamburg-Eppendorf, Institute of Pathology, Hamburg, Germany (GRID:grid.13648.38) (ISNI:0000 0001 2180 3484)
7 Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany (GRID:grid.419548.5) (ISNI:0000 0000 9497 5095)
8 Medical University of Vienna, Department of Laboratory Medicine, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492)
9 Humboldt-University and the Berlin Institute of Health, Department of Ophthalmology, Charité –University Medicine Berlin, a Corporate Member of Free University, Berlin, Germany (GRID:grid.484013.a)
10 Friedrich Schiller University, Institute for Nutritional Sciences, Jena, Germany (GRID:grid.9613.d) (ISNI:0000 0001 1939 2794)
11 University of Colorado Anschutz Medical Campus, Division of Rheumatology, Department of Medicine, Aurora, United States of America (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X)
12 Leibniz Institute for Natural Product Research and Infection Biology, Department of Infection Biology, Jena, Germany (GRID:grid.418398.f) (ISNI:0000 0001 0143 807X); Friedrich Schiller University, Faculty of Biosciences, Jena, Germany (GRID:grid.9613.d) (ISNI:0000 0001 1939 2794)