Journal: bioRxiv

Article Title: Antibody recycling via FcRn drives atherosclerotic plaque vulnerability

doi: 10.64898/2026.03.08.710352

Figure Lengend Snippet: Spatial distribution of immunoglobulins in human atherosclerotic plaques. ( A ) Representative formalin-fixed paraffin-embedded (FFPE) carotid plaque sections stained for IgA, IgE, IgM, and IgG, with quantification of total antibody-positive area per plaque. ( B ) Regional analysis of antibody staining in core, shoulder, and fibrous cap compartments (repeated-measures one-way ANOVA with Tukey’s post hoc test; n = 8 plaques). ( C ) Representative CD79A staining highlighting intraplaque B cells, with frequency of B-cell detection across samples. Data are presented as mean ± SD and scale bars as indicated.

Article Snippet: Cells were treated with 10 μg/ml rozanolixizumab (anti-human FcRn; HY-P9979, MedChemExpress) or an IgG4 isotype control (HY-P99003, MedChemExpress).

Techniques: Formalin-fixed Paraffin-Embedded, Staining

Journal: bioRxiv

Article Title: Antibody recycling via FcRn drives atherosclerotic plaque vulnerability

doi: 10.64898/2026.03.08.710352

Figure Lengend Snippet: Local IgG deposition associates with markers of atherosclerotic plaque vulnerability. ( A ) Heatmap showing correlations between IgG staining and morphological features of plaque vulnerability; Spearman r-values are displayed for significant correlations. ( B ) Representative micrographs illustrating the assessed morphological features. ( C ) Stratification of plaques into IgG-poor (<33% IgG⁺ area) and IgG-rich (>33% IgG⁺ area) groups. ( D ) Representative cap-region micrographs from IgG-poor and IgG-rich plaques; colored arrows indicate cap structure, and black arrows denote measured cap thickness. ( E ) Quantification of collagen content, cap thickness, and vulnerability index in IgG-rich versus IgG-poor plaques (unpaired t- test). ( F ) Computer tomography-based quantification of lipid-rich necrotic core, minimal cap thickness, and vulnerability index in IgG-rich versus IgG-poor plaques (Mann-Whitney test). Data are presented as mean ± SD and scale bars as indicated.

Article Snippet: Cells were treated with 10 μg/ml rozanolixizumab (anti-human FcRn; HY-P9979, MedChemExpress) or an IgG4 isotype control (HY-P99003, MedChemExpress).

Techniques: Staining, Tomography, MANN-WHITNEY

Journal: bioRxiv

Article Title: Antibody recycling via FcRn drives atherosclerotic plaque vulnerability

doi: 10.64898/2026.03.08.710352

Figure Lengend Snippet: Dynamic accumulation of apoB-specific IgG in human atherosclerotic plaques. ( A ) Associations between immunoglobulin concentrations and apoB levels in carotid plaque protein extracts. ( B ) Anti-apoB IgG levels measured in paired plasma and plaque samples normalized to 1 µg/ml total IgG (paired t -test). ( C ) Plaque anti-apoB IgG levels in asymptomatic versus symptomatic patients (unpaired t -test). ( D ) Schematic illustration of apoB, anti-apoB IgG, and apoB-IgG immune complexes. ( E ) Plaque apoB concentrations (unpaired t -test). ( F ) Levels of apoB-IgG immune complexes in plaques (unpaired t- test). ( G ) Matrix illustrating relationships among these parameters in asymptomatic (lower left) and symptomatic (upper right) patients. RLU, relative light units. Data are presented as mean ± SD.

Article Snippet: Cells were treated with 10 μg/ml rozanolixizumab (anti-human FcRn; HY-P9979, MedChemExpress) or an IgG4 isotype control (HY-P99003, MedChemExpress).

Techniques: Clinical Proteomics

Journal: bioRxiv

Article Title: Antibody recycling via FcRn drives atherosclerotic plaque vulnerability

doi: 10.64898/2026.03.08.710352

Figure Lengend Snippet: Expression of the IgG recycling receptor FcRn in plaque macrophages. ( A ) FCGRT expression in carotid plaques compared with non-diseased iliac arteries (unpaired t -test). Data are presented with median levels indicated. ( B ) Immunofluorescence staining of FcRn and CD163⁺ macrophages in the shoulder region of a carotid plaque. ( C ) Integrated single-cell RNA-seq analysis of myeloid populations in human atherosclerosis with a feature plot showing FCGRT expression (n = 26). ( D ) Age distribution in the carotid stenosis cohort and Spearman correlations between macrophage subset markers and patient age. Mac, macrophage; cDC, conventional dendritic cell; infla, inflammatory.

Article Snippet: Cells were treated with 10 μg/ml rozanolixizumab (anti-human FcRn; HY-P9979, MedChemExpress) or an IgG4 isotype control (HY-P99003, MedChemExpress).

Techniques: Expressing, Immunofluorescence, Staining, Single Cell, RNA Sequencing

Journal: bioRxiv

Article Title: Antibody recycling via FcRn drives atherosclerotic plaque vulnerability

doi: 10.64898/2026.03.08.710352

Figure Lengend Snippet: FcRn blockade or knockdown suppresses IgG recycling and inflammatory activation in macrophages. ( A ) Formation of LDL-IgG immune complexes in vitro using mouse IgG reactive against LDL. ( B ) Effects of Fcgrt knockdown in RAW 264.7 macrophages on IgG recycling and cytokine secretion, along with uptake of fluorescently labeled LDL (one-way ANOVA with Holm-Šídák correction). ( C ) Schematic of the THP-1 macrophage system used to assess the impact of rozanolixizumab on FcRn-dependent handling of immune complexes formed with plaque-derived IgG. ( D ) FcRn blockade reduces IgG1 recycling, TNF secretion, and alters uptake of fluorescently labeled LDL in THP-1 macrophages (one-way ANOVA with Holm-Šídák correction). MFI, mean fluorescence intensity; RQ, relative quantification. Data are presented with mean levels indicated.

Article Snippet: Cells were treated with 10 μg/ml rozanolixizumab (anti-human FcRn; HY-P9979, MedChemExpress) or an IgG4 isotype control (HY-P99003, MedChemExpress).

Techniques: Knockdown, Activation Assay, In Vitro, Labeling, Derivative Assay, Fluorescence, Quantitative Proteomics

Journal: bioRxiv

Article Title: Antibody recycling via FcRn drives atherosclerotic plaque vulnerability

doi: 10.64898/2026.03.08.710352

Figure Lengend Snippet: FcRn-dependent IgG recycling promotes MMP-9 production in macrophages and human plaques. ( B ) Silencing Fcgrt reduces MMP-9 production in RAW 264.7 macrophages stimulated with LDL immune complexes (unpaired t -test). ( C ) FcRn blockade with rozanolixizumab lowers MMP-9 production in LDL immune complex-stimulated THP-1 macrophages (unpaired t -test). ( D ) MMP-9 levels positively correlate with antibody concentrations in carotid plaques; Spearman r-values are shown for significant associations. ( E ) FCGRT transcript levels correlate with markers of plaque stability and vulnerability in carotid plaque tissue. ( F ) Ex vivo stimulation of human carotid plaques for 24 hours: IgG and MMP-9 were measured in plaque extracts, and TNF was quantified in supernatants (ratio paired t -test). AU, arbitrary units; RQ, relative quantification; AS, asymptomatic; S, symptomatic. Data are presented as mean ± SD.

Article Snippet: Cells were treated with 10 μg/ml rozanolixizumab (anti-human FcRn; HY-P9979, MedChemExpress) or an IgG4 isotype control (HY-P99003, MedChemExpress).

Techniques: Ex Vivo, Quantitative Proteomics

Journal: Frontiers in Cardiovascular Medicine

Article Title: NF- κ B aggravates cardiac vascular endothelial injury by sustained activation of the NLRP3 inflammasome after ischemic stroke in rats

doi: 10.3389/fcvm.2026.1673693

Figure Lengend Snippet: Brain ischemia induces sustained activation and inflammation of ECs in the heart. (A) GO biological process enrichment bubble chart of cardiac vascular tissues from Sham and dMCAO 2 w rats. (B) KEGG pathway enrichment bubble chart in cardiac vascular of Sham and dMCAO 2 w rats. (C) Heatmap of the relative protein levels of target proteins in NF- κ B signaling pathway. (D) The mRNA levels of p105, VCAM-1, ICAM-1, IL-1β and TNF-α in each group. (E) Western blotting shows the expression of p-p65, p65 , VCAM-1, ICAM-1, IL-1β, and TNF-α in vessels of the heart in the Sham and dMCAO animals. (F–J) Quantitative analysis of p-p65, VCAM-1, ICAM-1, IL-1β, and TNF-α levels relative to GAPDH. Each bar represents the mean ± SD. * p < 0.05 vs. Sham group ( n = 4 in each group). Sham, sham operation; dMCAO, distal middle cerebral artery occlusion; VCAM-1, vascular cell adhesion molecule 1; ICAM-1, intercellular cell adhesion molecule-1; IL-1β, interleukin-1 beta; TNF-α, tumor necrosis factor-alpha; w, week.

Article Snippet: The NLRP3-selective inflammasome inhibitor MCC950 (MedChemExpress, HY-12815A), the NF- κ B p65 inhibitor PDTC (MedChemExpress, HY-18738), or the vehicle (normal saline, NS) was injected intraperitoneally 24 h before dMCAO.

Techniques: Activation Assay, Western Blot, Expressing

Journal: Frontiers in Cardiovascular Medicine

Article Title: NF- κ B aggravates cardiac vascular endothelial injury by sustained activation of the NLRP3 inflammasome after ischemic stroke in rats

doi: 10.3389/fcvm.2026.1673693

Figure Lengend Snippet: PDTC inhibits the activation of NF- κ B signaling pathway and alleviates the activation of cardiac vascular endothelial cells after dMCAO. (A) Western blotting shows the expression of p-p65 and p65 in vessels of the heart in the Sham and dMCAO rats injected with Veh or PDTC. (B,C) Quantitative analysis of p-p65 and p65 levels relative to GAPDH. Each bar represents the mean ± SD. * p < 0.05 vs. Sham group, # p < 0.05 vs. dMCAO 2 w + Veh group ( n = 4 in each group). (D) Western blotting shows the expression of NLRP3, ASC, and Casp-1 in vessels of the heart in the Sham and dMCAO rats injected with Veh or PDTC. (E–G) Quantitative analysis of NLRP3, ASC, and Casp-1 levels relative to GAPDH. Each bar represents the mean ± SD. * p < 0.05 vs. Sham group, # p < 0.05 vs. dMCAO 2 w + Veh group ( n = 4 in each group). (H) The mRNA levels of VCAM-1, ICAM-1, IL-1β, and TNF-α in each group. (I) Western blotting shows the expression of VCAM-1, ICAM-1, IL-1β, and TNF-α in vessels of the heart in the Sham and dMCAO rats injected with Veh or PDTC. (J–M) Quantitative analysis of VCAM-1, ICAM-1, IL-1β, and TNF-α levels relative to GAPDH. Each bar represents the mean ± SD. * p < 0.05 vs. Sham group, # p < 0.05 vs. dMCAO 2 w + Veh group ( n = 4 in each group). Sham, sham operation; dMCAO, distal middle cerebral artery occlusion; NLRP3, NOD-like receptor thermal protein domain associated protein 3; ASC, apoptosis-associated speck-like protein containing a CARD; Casp-1, caspase-1; Veh, Vehicle; RECA-1, rat endothelial cell antibody 1; VCAM-1, vascular cell adhesion molecule 1; ICAM-1, intercellular cell adhesion molecule-1; IL-1β, interleukin-1 beta; TNF-α, tumor necrosis factor-alpha; w, week.

Article Snippet: The NLRP3-selective inflammasome inhibitor MCC950 (MedChemExpress, HY-12815A), the NF- κ B p65 inhibitor PDTC (MedChemExpress, HY-18738), or the vehicle (normal saline, NS) was injected intraperitoneally 24 h before dMCAO.

Techniques: Activation Assay, Western Blot, Expressing, Injection

Journal: Frontiers in Cardiovascular Medicine

Article Title: NF- κ B aggravates cardiac vascular endothelial injury by sustained activation of the NLRP3 inflammasome after ischemic stroke in rats

doi: 10.3389/fcvm.2026.1673693

Figure Lengend Snippet: PDTC inhibits the activation of NF- κ B signaling pathway. (A) Representative photomicrographs show the co-localization of p-p65 (green) and RECA-1 (red) in heart in the Sham and dMCAO rats injected with Veh or PDTC. (B) The degree of overlap between p-p65 and RECA-1 fluorescence based on the Pearson correlation coefficient in each group. (C) Quantitative analysis of CD45 + cells in each group. Each bar represents the mean ± SD. * p < 0.05 vs. Sham group, # p < 0.05 vs. dMCAO 2 w + Veh group ( n = 6 in each group).

Article Snippet: The NLRP3-selective inflammasome inhibitor MCC950 (MedChemExpress, HY-12815A), the NF- κ B p65 inhibitor PDTC (MedChemExpress, HY-18738), or the vehicle (normal saline, NS) was injected intraperitoneally 24 h before dMCAO.

Techniques: Activation Assay, Injection, Fluorescence

Journal: Frontiers in Cardiovascular Medicine

Article Title: NF- κ B aggravates cardiac vascular endothelial injury by sustained activation of the NLRP3 inflammasome after ischemic stroke in rats

doi: 10.3389/fcvm.2026.1673693

Figure Lengend Snippet: Knockdown of p65 in vessels of the heart inhibits the activation of NF- κ B signaling pathway and the activation of vascular endothelial cells after dMCAO. (A) Design of experiments in which rats were injected with NF- κ B adeno-associated virus vectors in tail vein and subjected to either Sham or dMCAO. (B) Representative photomicrographs show the co-localization of GFP (green) and RECA-1 (red) in heart from dMCAO rats with AAV- shNF-κB injection. Scale bar: 25 μm. The degree of overlap between GFP and RECA-1 fluorescence based on the Pearson correlation coefficient in dMCAO 2 w rats. (C) Representative NeuN staining indicates the cortical infarction. Scale bar: 2 mm. (D) Quantitative analysis of the relative infarct volumes. Each bar represents the mean ± SD. * p < 0.05 vs. Sham group ( n = 6 in each group). (E) Western blotting shows the expression of p-p65 and p65 in vessels of the heart in the Sham and dMCAO rats injected with AAV-shCon or AAV- shNF-κB . (F,G) Quantitative analysis of p-p65 and p65 levels relative to GAPDH. Each bar represents the mean ± SD. * p < 0.05 vs. Sham group, # p < 0.05 vs. dMCAO 2 w + AAV-shCon group ( n = 4 in each group). (H) Western blotting shows the expression of NLRP3, ASC, Casp-1, VCAM-1, ICAM-1, IL-1β, and TNF-α in vessels of the heart in the Sham and dMCAO rats injected with AAV-shCon or AAV- shNF-κB . (I–O) Quantitative analysis of NLRP3, ASC, Casp-1, VCAM-1, ICAM-1, IL-1β, and TNF-α levels relative to GAPDH. Each bar represents the mean ± SD. * p < 0.05 vs. Sham group, # p < 0.05 vs. dMCAO 2 w + AAV-shCon group ( n = 4 in each group).Sham, sham operation; dMCAO, distal middle cerebral artery occlusion; GFP, green fluorescent protein; NLRP3, NOD-like receptor thermal protein domain associated protein 3; ASC, apoptosis-associated speck-like protein containing a CARD; Casp-1, caspase-1; Veh, Vehicle; RECA-1, rat endothelial cell antibody 1; VCAM-1, vascular cell adhesion molecule 1; ICAM-1, intercellular cell adhesion molecule-1; IL-1β, interleukin-1 beta; TNF-α, tumor necrosis factor-alpha; w, week.

Article Snippet: The NLRP3-selective inflammasome inhibitor MCC950 (MedChemExpress, HY-12815A), the NF- κ B p65 inhibitor PDTC (MedChemExpress, HY-18738), or the vehicle (normal saline, NS) was injected intraperitoneally 24 h before dMCAO.

Techniques: Knockdown, Activation Assay, Injection, Virus, Fluorescence, Staining, Western Blot, Expressing