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. 2025 May 20;14(10):e040911.
doi: 10.1161/JAHA.124.040911. Epub 2025 May 15.

AhR, IRF5, and HO-1 Expression in Evaluating Carotid Atherosclerotic Plaque Vulnerability: A Pilot Observational Study

Chiara Barisione  1   2 , Silvia Ortona  3 , Caterina Ivaldo  1 , Giada Righetti  2 , Fabio Pisa  1 , Jorge Miguel Mena Vera  3 , Marina Sartini  4   5 , Domenico Palombo  1 , Simona Pigozzi  1 , Davide Esposito  1   6 , Martina Bastianon  1 , Michele Paudice  1   2 , Valerio Gaetano Vellone  1   7 , Jasmin Ortolan  3 , Luca Giliberto  8   9 , Cristina d'Abramo  9 , Anna Lisa Furfaro  3 , Giovanni Pratesi  1   6 , Mariapaola Nitti  2   3
Affiliations

AhR, IRF5, and HO-1 Expression in Evaluating Carotid Atherosclerotic Plaque Vulnerability: A Pilot Observational Study

Chiara Barisione et al. J Am Heart Assoc. .
No abstract available

Keywords: IRF5; ROC curve; aryl hydrocarbon receptor; atherosclerotic plaque; carotid stenosis; heme oxygenase 1; maladaptive inflammation.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1. Evaluation of aryl hydrocarbon receptor, interferon regulatory factor 5, and heme oxygenase‐1 expression in samples from asymptomatic and symptomatic patients.
A, AhR and IRF5 mRNA analysis in PBMCs (RT‐qPCR). First and second graphs show AhR and IRF5 mRNA expression in asymptomatic (blue) and symptomatic (red) patients expressed as median with IQR (Mann–Whitney test). The third graph shows their correlation (Spearman's test); “r” and “P” values (Monte Carlo permutations) are indicated for each subgroup (asymptomatic patients=blue, symptomatic patients=red, whole population=black). The same statistical analyses and color codes are used in (B through E). (B) HO‐1 and IRF5 mRNA analysis in PBMCs (RT‐qPCR). The first graph shows HO‐1 mRNA expression in PBMCs in asymptomatic and symptomatic patients. The second graph shows the correlation of HO‐1 and IRF5 mRNA expression. (C) HO‐1 serum levels. Graph shows HO‐1 serum content in asymptomatic and symptomatic patients, as detected by ELISA assay (pg/mL). (D) AhR immunopositivity (IHC) in tissue samples. Scale bars are 3 mm for the whole lesion and 200 μm for shoulder‐neovasa. Shoulder refers to the portion of the lesion corresponding to the periphery of the lipid core. Boxes indicate inflammatory infiltrates and neovasa (40× magnification, scale bar=60 μm). The graphs below show the quantification of AhR immunopositivity in lesions retrieved from asymptomatic and symptomatic patients. (E) Correlation between AhR immunopositivity in tissue samples and IRF5 mRNA expression in PBMCs. The graph shows the correlation between the quantification of AhR immunopositivity in the whole lesion and IRF5 mRNA expression in PBMCs in asymptomatic and symptomatic patients. (F) ROC curves. ROC curves were used to calculate the ability of AhR, IRF5, and HO‐1, or their joint evaluation, to identify symptomatic patients. Orange line: HO‐1 serum level (asympto n=46, sympto n=22, AUC=0.5879, 95% CI 0.4333 to 0.7426). Green line: IRF5 mRNA expression (asympto n=43, sympto n=21, AUC=0.6307, 95% CI 0.4791 to 0.7833). Violet line: AhR mRNA expression (asympto n=45, sympto n=22, AUC=0.6556, 95% CI 0.5002 to 0.8109). Blue line: post‐multivariate logistic regression ROC for simultaneous detection of IRF5 and AhR mRNA expression in PBMCs and HO‐1 serum levels (asympto n=42, sympto n=21, AUC=0.7041, 95% CI 0.5467 to 0.8615). DeLong's test was used to evaluate uncertainty in AUC differences: AhR vs IRF5, AhR, HO‐1: delta AUC=−0.047, SE=0.035, 95% CI −0.114 to 0.021. IRF5 vs IRF5, AhR, HO‐1: delta AUC=−0.072, SE=0.057, 95% CI −0.183 to 0.040. HO‐1 vs IRF5, AhR, HO‐1: delta AUC=−0.114, SE=0.088, 95% CI −0.282 to 0.061. AhR indicates aryl hydrocarbon receptor; AU, arbitrary unit; AUC, area under the curve; HO‐1, heme oxygenase 1; IRF5, interferon regulatory factor 5; IQR, interquartile range; PBMCs, peripheral blood mononuclear cells; and RT‐qPCR, reverse transcription–quantitative polymerase chain reaction.
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