Abstract Body: Background
Atherosclerosis is characterized by plaque formation in arterial walls, causing narrowing and increasing cardiovascular risk, primarily driven by monocyte–endothelial interactions. CD93, a C-type lectin-like transmembrane glycoprotein, plays diverse roles in cell adhesion and immune regulation, with its soluble form (sCD93) implicated in metabolic regulation and cardiovascular diseases. This study investigated the protective role of recombinant extracellular domain of CD93 (rCD93D123) in atherosclerosis by modulating endothelial-monocyte interactions.
Methods
Recombinant CD93D123 was produced using a mammalian protein expression system. We utilized flow cytometry to analyze the binding of rCD93D123 to endothelial cells and performed permeability assays to assess endothelial integrity. The influence of rCD93D123 on endothelial-monocyte interaction was examined using real-time and static monocyte adhesion, as well as trans-endothelial migration test. In vivo, rCD93D123 (0.45 mg/kg intraperitoneally) was tested in a thioglycollate-induced peritonitis model and apolipoprotein E deficient (ApoE^–/–) mice fed a Western-type diet (WD) for 16 weeks (n=3–5 per group) to evaluate its impact on macrophage recruitment and atherosclerotic plaque burden.
Results
Recombinant CD93D123 dose-dependently bound the activated endothelial cells and significantly reduced monocyte adhesion and transmigration while preserving endothelial barrier integrity. In vivo, rCD93D123 significantly inhibited macrophage infiltration (control: 52.8% ± 2.7% vs. treatment: 39.8% ± 8.2%) without affecting neutrophil recruitment in the peritonitis model. ApoE^–/– mice on a WD exhibited elevated sCD93 levels compared to those on a normal diet (269.9 ± 32.0 ng/mL vs. 152.4 ± 19.5 ng/mL, P < 0.001). In the atherosclerosis model, treatment with rCD93D123 did not alter lipid profiles or sCD93 levels but significantly ameliorated atherosclerotic lesion formation (control: 53.3% ± 2.0% versus treatment: 35.9% ± 4.5%, P < 0.01).
Conclusion
In summary, rCD93D123 attenuates macrophage recruitment and atherosclerotic plaque formation, underscoring its potential as a novel anti-inflammatory strategy for vascular disease.