Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque
Tomohiro Komatsu1, Makoto Ayaori1,2, Harumi Uto-Kondo1
1Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College.
Insights
Atorvastatin significantly reduced arterial inflammation, lowering C-reactive protein (CRP) and S100A12 levels. These findings suggest S100A12 as a potential therapeutic target for atherosclerosis.
Area of Science:
- Cardiovascular Research
- Inflammation Biology
- Pharmacology
Background:
- Inflammation plays a key role in atherosclerosis development.
- Serum C-reactive protein (CRP) is a cardiovascular risk predictor, often reduced by statins.
- The impact of statins on S100A12, another inflammatory marker, in atherosclerosis is unclear.
Purpose of the Study:
- To investigate the effect of atorvastatin on arterial inflammation and S100A12 levels.
- To identify biomarkers correlated with changes in arterial inflammation.
- To explore S100A12 as a potential therapeutic target for atherosclerosis.
Main Methods:
- Prospective, randomized open-label trial involving 31 statin-naïve patients with carotid plaques.
- Intervention groups: dietary management vs. atorvastatin (10mg/day) for 12 weeks.
- Assessment methods: 18F-FDG-PET/CT for arterial inflammation, flow-mediated vasodilation (FMD) for endothelial function, and serum inflammatory markers.
Main Results:
- Atorvastatin significantly reduced LDL-cholesterol, CRP, and S100A12 levels, and improved FMD.
- 18F-FDG-PET/CT showed reduced arterial inflammation in the carotid and thoracic aorta with atorvastatin.
- Multivariate analysis linked reductions in CRP, S100A12, LDL-C, and oxidized-LDL, along with increased FMD, to reduced thoracic aorta inflammation.
Conclusions:
- Atorvastatin treatment effectively reduced arterial inflammation, S100A12, and CRP levels.
- Changes in circulating S100A12 and CRP mirrored improvements in arterial inflammation.
- S100A12 emerges as a promising therapeutic target for managing atherosclerosis.
Aims:
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.
Methods:
We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using 18fluorodeoxyglucose positron emission tomography/computed tomography (18F-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. 18F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function.
Results:
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%). 18F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of 18F-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.
Conclusions:
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.
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