Abstract 2021: Aspirin Treatment Increases Scavenger Receptor Class B Type I Protein Expression in Human Carotid Atherosclerotic Plaques
Introduction and Hypothesis - We have recently shown that aspirin promotes scavenger receptor class B type I (SR-BI) protein expression in vitro in primary human macrophages and in vivo in resident macrophages of mice. We therefore assessed the hypothesis that aspirin may also influence macrophage SR-BI expression in vivo in humans.
Methods - After carotid endarterectomy, we compared SR-BI and macrophage-specific CD68 expression in carotid atherosclerotic specimens from patients without (n = 19) and with (n = 38) > 3 months of low-dose aspirin medication (100 – 200 mg/d). Gene and protein expression was analyzed using Taqman Real Time PCR and Western Blot analysis, respectively.
Results - No difference in the expression of SR-BI and CD68 was observed on the mRNA-level. However, taking into account presence or absence of atherosclerotic risk factors (smoking, diabetes, hyperlipidemia and hypertension) and medication in both groups of patients, SR-BI protein expression in plaques from patients who have received aspirin was significantly increased compared to patients without aspirin (+ 19.2 %, P = 0.046). CD68 protein expression did not differ significantly between these two groups (+ 6.7 % in patients with aspirin, P = 0.321). Finally, IκB-α protein, the physiological inhibitor of the transcription factor NF-κB, was also found increased in plaques from aspirin-treated patients (+ 149.4 %, P = 0.016), demonstrating possible involvement of nuclear NF-κB signaling in this scenario.
Conclusions - In conclusion, these data corroborate our findings describing a posttranscriptional mechanism of SR-BI regulation by aspirin: we show that aspirin indeed enhanced SR-BI protein, but not mRNA, levels in vivo in human atherosclerotic lesions. This may cause an enhanced efflux of cholesterol from lipid laden macrophages within the arterial wall and may therefore retard plaque progression.