Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College.
Tokorozawa Heart Center.
J Atheroscler Thromb. 2022 May 1;29(5):775-784. doi: 10.5551/jat.61630. Epub 2021 May 1.
Inflammation is involved in various processes of atherosclerosis development. Serum C-reactive protein (CRP) levels, a predictor for cardiovascular risk, are reportedly reduced by statins. However, several studies have demonstrated that CRP is a bystander during atherogenesis. While S100A12 has been focused on as an inflammatory molecule, it remains unclear whether statins affect circulating S100A12 levels. Here, we investigated whether atorvastatin treatment affected S100A12 and which biomarkers were correlated with changes in arterial inflammation.
We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT) and inflammatory markers. Thirty-one statin-naïve patients with carotid atherosclerotic plaques were randomized to either a group receiving dietary management (n=15) or one receiving atorvastatin (10mg/day, n=16) for 12weeks. F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function.
Atorvastatin, but not the diet-only treatment, significantly reduced LDL-cholesterol (LDL-C, -43%), serum CRP (-37%) and S100A12 levels (-28%) and improved FMD (+38%). F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of F-FDG in the carotid artery and thoracic aorta. A multivariate analysis revealed that reduction in CRP, S100A12, LDL-C, oxidized-LDL, and increase in FMD were significantly associated with reduced arterial inflammation in the thoracic aorta, but not in the carotid artery.
Atorvastatin treatment reduced S100A12/CRP levels, and the changes in these circulating markers mirrored the improvement in arterial inflammation. Our observations suggest that S100A12 may be an emerging therapeutic target for atherosclerosis.
炎症参与了动脉粥样硬化发展的各个过程。血清 C 反应蛋白（CRP）水平是心血管风险的预测因子，据报道他汀类药物可降低其水平。然而，一些研究表明 CRP 是动脉粥样形成过程中的旁观者。虽然 S100A12 已被视为炎症分子，但他汀类药物是否影响循环 S100A12 水平仍不清楚。在这里，我们研究了阿托伐他汀治疗是否会影响 S100A12 以及哪些生物标志物与动脉炎症的变化相关。
我们进行了一项前瞻性、随机、开放性临床试验，研究阿托伐他汀是否通过氟代脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（F-FDG-PET/CT）和炎症标志物影响动脉（颈动脉和胸主动脉）炎症。31 名他汀类药物初治颈动脉粥样硬化斑块患者被随机分为接受饮食管理组（n=15）或阿托伐他汀组（10mg/天，n=16）治疗 12 周。进行 F-FDG-PET/CT 和血流介导的血管扩张（FMD），后者用于评估内皮功能。
阿托伐他汀治疗而非单纯饮食治疗显著降低 LDL 胆固醇（LDL-C，-43%）、血清 CRP（-37%）和 S100A12 水平（-28%），并改善 FMD（+38%）。F-FDG-PET/CT 显示，阿托伐他汀治疗而非单纯饮食治疗显著减少颈动脉和胸主动脉 F-FDG 的积累。多变量分析显示，CRP、S100A12、LDL-C、氧化 LDL 的降低以及 FMD 的增加与胸主动脉而非颈动脉的动脉炎症减轻显著相关。
阿托伐他汀治疗降低了 S100A12/CRP 水平，这些循环标志物的变化反映了动脉炎症的改善。我们的观察结果表明，S100A12 可能是动脉粥样硬化的一个新的治疗靶点。
