Background: Vascular diseases are highly associated with inflammation and thrombosis. Elucidating links between these two processes may provide a clearer understanding of these diseases, allowing for the design of more effective treatments. The activation of complement component 1 (C1) is a crucial contributor to innate immunity and is associated with significant concentrations of circulating C1q. Many pathological pathways initiate when C1q interacts with gC1qR. This interaction plays a major role in inflammation observed during atherosclerosis and the initiation of intrinsic coagulation. However, the effects of C1 and the role of C1q/gC1qR on extrinsic coagulation, which is the more physiologically relevant coagulation arm, has not been studied. We hypothesized that C1q binding to gC1qR enhances the expression of tissue factor (TF) in adventitial fibroblasts and vascular smooth muscle cells, the primary TF bearing cells in the body.
Methods: Using an enzyme-linked immunosorbent assay approach, TF expression and the role of gC1qR was observed. Cells were conditioned for 1 h with C1q or a gC1qR blocker and C1q, to assess the role of gC1qR. Additionally, cell growth characteristics were monitored to assess changes in viability and metabolic activity.
Results: Our results indicate that the expression of TF increased significantly after incubation with C1q as compared with unconditioned cells. Cells conditioned with gC1qR blockers and C1q exhibited no change in TF expression when compared with cells conditioned with the blocking antibodies alone. Our results show no significant differences in metabolic activity or cell viability under these conditions.
Conclusions: This indicates that gC1qR association with C1q induces TF expression and may initiate extrinsic coagulation. Overall, this data illustrates a role for C1q in the activation of extrinsic coagulation and that gC1qR activity may link inflammation and thrombosis.
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http://dx.doi.org/10.1002/iid3.769 | DOI Listing |
Toxins (Basel)
January 2025
Institute of Biomedicine, Hubei Key Laboratory of Embryonic Stem Cell Research, College of Basic Medicine, Hubei University of Medicine, Shiyan 442000, China.
Coagulation factor XIa is a new serine-protease family drug target for next-generation anticoagulants. With the snake venom Kunitz-type peptide BF9 as the scaffold, we obtained a highly active XIa inhibitor BF9-N17K in our previous work, but it also inhibited the hemostatic target plasmin. Here, in order to enhance the selectivity of BF9-N17K toward XIa, four mutants, BF9-N17K-L19A, BF9-N17K-L19S, BF9-N17K-L19D, and BF9-N17K-L19K, were further designed using the P2' amino acid classification scanning strategy.
View Article and Find Full Text PDFCarbohydr Polym
March 2025
Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address:
The development of self-elastic sponges with enhanced hemostatic and antibacterial properties to treat noncompressible hemorrhage and facilitate wound healing remains challenging. Herein, we prepared a chitosan sponge reinforced with lauric acid-modified quaternized chitosan (LQC) and attapulgite, features a porous structure, high self-elasticity, and rapid shape recovery. The incorporation of LQC conferred the sponge with an enhanced capacity to promote the adhesion, aggregation, and activation of blood cells, and resistance to infection by Staphylococcus aureus, Escherichia coli, and Methicillin-resistant Staphylococcus aureus; the incorporation of attapulgite enhanced the hydrophilicity and mechanical strength of the sponge, and its ability to activate the intrinsic and extrinsic coagulation pathways.
View Article and Find Full Text PDFFundam Clin Pharmacol
February 2025
Experimental Oncology and Hemopathies Laboratory, Clinical Analysis Department, Federal University of Santa Catarina, Florianópolis, 88040-900, Brazil.
Background: Chalcones have been described in the literature as promising antineoplastic compounds.
Objectives: Therefore, the objective of this study was to analyze the cytotoxic effect of 23 synthetic chalcones on human acute leukemia (AL) cell lines (Jurkat and K562).
Methods: Cytotoxicity assessment was performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method.
Sci Rep
January 2025
Department of Emergency Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
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