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Tafolecimab mitigates ox‑LDL‑induced macrophage foam cell formation and inflammation by modulating SR‑A/ABCG1 expression and inhibiting the NF‑κB/MAPK pathways

  • Authors:
    • Xinyi Yu
    • Xiaodan Liu
    • Yuanye Dang
    • Ruoxuan Liu
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510645, P.R. China, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, Guangdong 510623, P.R. China, Key Laboratory of Molecular Target and Clinical Pharmacology, The Affiliated Traditional Chinese Medicine Hospital, NMPA and State Key Laboratory of Respiratory Diseases, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
    Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 116
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    Published online on: August 13, 2026
       https://doi.org/10.3892/br.2026.2189
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Abstract

Macrophage foam‑cell formation, triggered by excessive uptake of oxidized low‑density lipoprotein (ox‑LDL) and subsequent intracellular lipid accumulation, represents a critical pathological event in atherosclerotic plaque initiation that drives localized inflammatory responses. The present study investigated the effects of tafolecimab on ox‑LDL‑induced foam‑cell formation and inflammatory responses in murine macrophages, and further explored the underlying molecular mechanisms. Foam‑cell models were established by exposing RAW264.7 cells to 100 µg/ml ox‑LDL for 24 h. The study groups included a blank control group, a model group, low‑, medium‑ and high‑dose tafolecimab groups (5, 10 and 20 µmol/l, respectively), and a positive control group treated with evolocumab. Intracellular lipid accumulation and cholesterol levels were evaluated using Oil Red O staining and a low‑density lipoprotein‑cholesterol (LDL‑C) assay kit. Western blot analysis was performed to determine the expression of cholesterol metabolism‑related proteins [class A scavenger receptor (SR‑A) and ATP‑binding cassette subfamily G member 1 (ABCG1)] and key components of the nuclear factor‑κB (NF‑κB)/mitogen‑activated protein kinase (MAPK) signaling pathways (NF‑κB p65 and phosphorylated p38). The concentrations of the inflammatory cytokines tumor necrosis factor‑α (TNF‑α) and interleukin‑6 (IL‑6) in the cell supernatant were quantified by enzyme‑linked immunosorbent assay. Compared with the blank control, ox‑LDL treatment markedly increased intracellular lipid‑droplet accumulation and LDL‑C content, confirming the successful establishment of a foam‑cell model. In vitro, compared with the model group, tafolecimab reduced intracellular lipid accumulation and cholesterol content in a dose‑dependent manner (P<0.001). In addition, tafolecimab significantly decreased the expression of the cholesterol influx receptor SR‑A while increasing that of the cholesterol efflux transporter ABCG1 (P<0.001). Furthermore, it effectively inhibited the phosphorylation of NF‑κB p65 and MAPK p38, which was accompanied by reduced secretion of TNF‑α and IL‑6 (P<0.001). The present results indicate that tafolecimab inhibits ox‑LDL‑induced macrophage foam‑cell formation and inflammatory responses, likely by modulating the balance between SR‑A‑mediated cholesterol influx and ABCG1‑mediated cholesterol efflux in favor of cholesterol efflux, and by inhibiting NF‑κB and MAPK pathway activation.
View Figures

Figure 1

Oil Red O staining of cells treated
with different drug concentrations. (A-E) Tafolecimab treatment
groups. (F-J) Evolocumab treatment groups. The groups received the
following designated treatments: (A and F) Blank control group; (B
and G) model groups; (C) tafolecimab low-dose group; (H) evolocumab
low-dose group; (D) tafolecimab medium-dose group; (I) evolocumab
medium-dose group; (E) tafolecimab high-dose group; and (J)
evolocumab high-dose group.

Figure 2

Assessment of the therapeutic effects
of tafolecimab and evolocumab in an atherosclerosis model. Effects
of tafolecimab and evolocumab on lipid accumulation in
ox-LDL-treated macrophages. (A) Percentage of Oil Red O-positive
areas in macrophages treated with increasing concentrations of
tafolecimab. (B) Percentage of Oil Red O-positive areas in
macrophages treated with increasing concentrations of evolocumab.
Experimental groups included blank control (Control), ox-LDL model
(Model), and drug-treated groups with low (5 µmol/l), medium (10
µmol/l) and high (20 µmol/l) concentrations. Data are presented as
the mean ± standard deviation from three independent experiments.
One-way analysis of variance followed by Dunnett's post hoc test
was used for statistical analysis. ***P<0.001 vs. the
model group. Ox-LDL, oxidized low-density lipoprotein.

Figure 3

Effects of tafolecimab and evolocumab
on intracellular LDL-C levels in ox-LDL-treated macrophages. LDL-C
concentrations in macrophages treated with increasing doses of
tafolecimab. LDL-C concentrations in macrophages treated with
increasing doses of evolocumab. Experimental groups included a
blank control (Control), ox-LDL model (Model), and drug-treated
groups at low (5 µmol/l), medium (10 µmol/l) and high (20 µmol/l)
doses. Data are presented as the mean ± standard deviation (n=3).
One-way analysis of variance followed by Dunnett's post hoc test
was used for statistical analysis. *P<0.05 vs. the
model group. LDL-C, low-density lipoprotein cholesterol; ox-LDL,
oxidized low-density lipoprotein.

Figure 4

Effects of tafolecimab and evolocumab
on ABCG1 and SR-A protein expression in ox-LDL-stimulated
macrophages. (A and B) Representative western blot images showing
(A) ABCG1 and (B) SR-A protein levels in macrophages treated with
ox-LDL in the absence or presence of tafolecimab or evolocumab (5,
10, and 20 µmol/l). GAPDH was used as a loading control. Molecular
weights are indicated on the right. (C and D) Quantitative analysis
of (A) ABCG1 and (B) SR-A protein expression normalized to GAPDH
and expressed as the relative intensity compared with the model
group. (E and F) Trend analysis of (E) ABCG1 and (F) SR-A relative
protein density across treatment groups. Data are presented as the
mean ± standard deviation from three independent experiments.
Statistical significance was determined by one-way ANOVA followed
by Dunnett's post hoc test. *P<0.05,
**P<0.01 and ***P<0.001. ABCG1,
ATP-binding cassette subfamily G member 1; SR-A, class A scavenger
receptor; ox-LDL, oxidized low-density lipoprotein; Con, control;
Mol, ox-LDL model group.

Figure 5

Effects of tafolecimab and evolocumab
on p38 and p65 phosphorylation in ox-LDL-stimulated macrophages.
(A) Representative western blot images showing the protein
expression levels of p-p38, total p38, p-p65, and total p65 in
macrophages stimulated with ox-LDL and treated with tafolecimab or
evolocumab at indicated concentrations (5, 10, and 20 µmol/l).
Vinculin and tubulin were used as loading controls. Molecular
weights are indicated on the right. (B and C) Quantitative analysis
of (B) p-p38 (B) and (C) p-p65 protein levels, normalized to their
respective total proteins (p38 or p65) and expressed as relative
intensity compared with the model group. (D and E) Trend analysis
of relative (D) p-p38 and (E) p-p65 protein expression across
treatment groups. Data are presented as the mean ± standard
deviation from three independent experiments. Statistical analysis
was performed using one-way ANOVA followed Dunnett's post hoc test.
*P<0.05, **P<0.01 and
***P<0.001. ox-LDL, oxidized low-density lipoprotein;
p-p38, phosphorylated p38; p-p65, phosphorylated p65; Con, control
group; Mol, ox-LDL model group.

Figure 6

Inhibitory effects of tafolecimab on
the secretion of the inflammatory cytokines TNF-α and IL-6. (A and
B) Cytokine levels in the cell supernatant were measured using
ELISA. (A) IL-6 concentration. (B) TNF-α concentration.
Experimental groups included low-, medium- and high-dose
tafolecimab and evolocumab groups. Blank control and model groups
were included for reference. Compared with the blank control group,
TNF-α and IL-6 levels in the model group were significantly
elevated (P<0.001). Tafolecimab treatment dose-dependently
suppressed the secretion of both cytokines (P<0.001). Data are
presented as the mean ± standard deviation (n=3). One-way analysis
of variance followed by Dunnett's post hoc test was used for
statistical analysis. ***P<0.001 vs. the model
group.
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Copy and paste a formatted citation
Spandidos Publications style
Yu X, Liu X, Dang Y and Liu R: Tafolecimab mitigates ox‑LDL‑induced macrophage foam cell formation and inflammation by modulating SR‑A/ABCG1 expression and inhibiting the NF‑&kappa;B/MAPK pathways. Biomed Rep 25: 116, 2026.
APA
Yu, X., Liu, X., Dang, Y., & Liu, R. (2026). Tafolecimab mitigates ox‑LDL‑induced macrophage foam cell formation and inflammation by modulating SR‑A/ABCG1 expression and inhibiting the NF‑&kappa;B/MAPK pathways. Biomedical Reports, 25, 116. https://doi.org/10.3892/br.2026.2189
MLA
Yu, X., Liu, X., Dang, Y., Liu, R."Tafolecimab mitigates ox‑LDL‑induced macrophage foam cell formation and inflammation by modulating SR‑A/ABCG1 expression and inhibiting the NF‑&kappa;B/MAPK pathways". Biomedical Reports 25.4 (2026): 116.
Chicago
Yu, X., Liu, X., Dang, Y., Liu, R."Tafolecimab mitigates ox‑LDL‑induced macrophage foam cell formation and inflammation by modulating SR‑A/ABCG1 expression and inhibiting the NF‑&kappa;B/MAPK pathways". Biomedical Reports 25, no. 4 (2026): 116. https://doi.org/10.3892/br.2026.2189
Copy and paste a formatted citation
x
Spandidos Publications style
Yu X, Liu X, Dang Y and Liu R: Tafolecimab mitigates ox‑LDL‑induced macrophage foam cell formation and inflammation by modulating SR‑A/ABCG1 expression and inhibiting the NF‑&kappa;B/MAPK pathways. Biomed Rep 25: 116, 2026.
APA
Yu, X., Liu, X., Dang, Y., & Liu, R. (2026). Tafolecimab mitigates ox‑LDL‑induced macrophage foam cell formation and inflammation by modulating SR‑A/ABCG1 expression and inhibiting the NF‑&kappa;B/MAPK pathways. Biomedical Reports, 25, 116. https://doi.org/10.3892/br.2026.2189
MLA
Yu, X., Liu, X., Dang, Y., Liu, R."Tafolecimab mitigates ox‑LDL‑induced macrophage foam cell formation and inflammation by modulating SR‑A/ABCG1 expression and inhibiting the NF‑&kappa;B/MAPK pathways". Biomedical Reports 25.4 (2026): 116.
Chicago
Yu, X., Liu, X., Dang, Y., Liu, R."Tafolecimab mitigates ox‑LDL‑induced macrophage foam cell formation and inflammation by modulating SR‑A/ABCG1 expression and inhibiting the NF‑&kappa;B/MAPK pathways". Biomedical Reports 25, no. 4 (2026): 116. https://doi.org/10.3892/br.2026.2189
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