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辛伐他汀对高胆固醇血症患者炎症和血小板活化标志物的影响。

Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia.

机构信息

Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.

Metabolic Diseases and Diabetes Unit, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.

出版信息

Biomed Res Int. 2018 Oct 1;2018:6508709. doi: 10.1155/2018/6508709. eCollection 2018.

Abstract

BACKGROUND

Beside the lipid-lowering effect, statins slow the progression of atherosclerosis by exerting anti-inflammatory and platelet inhibiting effects. We investigated whether platelet inhibition by simvastatin correlates with the statin effects on lipid lowering, inflammation, oxidative stress, and endothelial and platelet activation.

METHODS

In hypercholesterolemic patients allocated to diet (n=20) or a 2-month treatment with diet plus 40 mg simvastatin (n=25), we evaluated platelet aggregating responses to ADP, collagen, and arachidonic acid (AA), the effect of aspirin on AA-induced aggregation, pro- and anti-inflammatory and atherogenic mediators (IL-1, -5, -6, -7, -8, -9, -10, -12, and -13, IFN-, IP-10, Eotaxin, and sRAGE), markers of endothelium (sE-selectin, VEGF, and MCP-1) and platelet activation (sP-selectin, sCD-40L, RANTES, and PDGF-bb), and oxidative stress (8-OH-2'-deoxyguanosine).

RESULTS

After treatment, beside the improvement of lipid profile, we observed the following: a reduction of platelet aggregation to ADP (p=0.0001), collagen (p=0.0001), AA (p=0.003); an increased antiaggregating effect of aspirin in the presence of AA (p=0.0001); a reduction of circulating levels of IL-6 (p=0.0034), IL-13 (p<0.0001), IFN- (p<0.0001), VEGF (p<0.0001), sE-selectin (p<0.0001), sCD-40L (p<0.0001), sP-selectin (p=0.003), and 8-OH-2'-deoxyguanosine (p<0.0001); an increase of IL-10 and sRAGEs (p=0.0001 for both). LDL-cholesterol levels (i) positively correlated with IL-6, IFN-, E-selectin, sCD-40L, 8-OH-2'-deoxyguanosine, platelet aggregation to ADP, collagen, AA, and aspirin IC-50 and (ii) negatively correlated with IL-10 and sRAGE. In multiple regression analyses, LDL-cholesterol was the strongest predictor for most parameters of platelet reactivity.

CONCLUSION

In primary hypercholesterolemia, simvastatin treatment reduced platelet activation and subclinical inflammation and improved endothelial dysfunction. LDL-cholesterol levels were the major correlate of platelet reactivity; however, other effects of statins may contribute to reducing the progression of atherosclerosis.

摘要

背景

除了降脂作用外,他汀类药物还通过发挥抗炎和血小板抑制作用来减缓动脉粥样硬化的进展。我们研究了辛伐他汀对血小板的抑制作用是否与他汀类药物降低血脂、炎症、氧化应激以及内皮细胞和血小板激活的作用有关。

方法

在被分配到饮食治疗(n=20)或饮食加 40mg 辛伐他汀治疗 2 个月的高胆固醇血症患者(n=25)中,我们评估了血小板对 ADP、胶原和花生四烯酸(AA)的聚集反应,阿司匹林对 AA 诱导的聚集的影响,促炎和抗炎以及致动脉粥样硬化介质(IL-1、-5、-6、-7、-8、-9、-10、-12 和 -13、IFN-、IP-10、Eotaxin 和 sRAGE)、内皮细胞标志物(sE-选择素、VEGF 和 MCP-1)和血小板激活标志物(sP-选择素、sCD-40L、RANTES 和 PDGF-bb)以及氧化应激(8-OH-2'-脱氧鸟苷)的影响。

结果

治疗后,除了改善血脂谱外,我们还观察到:ADP(p=0.0001)、胶原(p=0.0001)、AA(p=0.003)的血小板聚集减少;AA 存在时阿司匹林的抗聚集作用增强(p=0.0001);循环 IL-6(p=0.0034)、IL-13(p<0.0001)、IFN-(p<0.0001)、VEGF(p<0.0001)、sE-选择素(p<0.0001)、sCD-40L(p<0.0001)、sP-选择素(p=0.003)和 8-OH-2'-脱氧鸟苷(p<0.0001)水平降低;IL-10 和 sRAGEs 增加(两者均为 p=0.0001)。LDL-胆固醇水平(i)与 IL-6、IFN-、E-选择素、sCD-40L、8-OH-2'-脱氧鸟苷、ADP、胶原、AA 诱导的血小板聚集和阿司匹林 IC50 呈正相关,(ii)与 IL-10 和 sRAGE 呈负相关。在多元回归分析中,LDL-胆固醇是血小板反应性的大多数参数的最强预测因子。

结论

在原发性高胆固醇血症中,辛伐他汀治疗可降低血小板活性和亚临床炎症,并改善内皮功能障碍。LDL-胆固醇水平是血小板反应性的主要相关因素;然而,他汀类药物的其他作用可能有助于减缓动脉粥样硬化的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90f1/6191949/9dc3d638053d/BMRI2018-6508709.001.jpg

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