A Clinical Evaluation of Statin Pleiotropy: Statins Selectively and Dose-Dependently Reduce Vascular Inflammation

作者：van der Meij Evelien; Koning Giel G; Vriens Patrick W; Peeters Marcel F; Meijer C Arnoud; Kortekaas Kim E; Dalman Ronald L; van Bockel J Hajo; Hanemaaijer Roeland; Kooistra Teake; Kleemann Robert; Lindeman Jan H N^*

来源：PLos One, 2013, 8(1): e53882.

DOI：10.1371/journal.pone.0053882

Statins are thought to reduce vascular inflammation through lipid independent mechanisms. Evaluation of such an effect in atherosclerotic disease is complicated by simultaneous effects on lipid metabolism. Abdominal aortic aneurysms (AAA) are part of the atherosclerotic spectrum of diseases. Unlike atherosclerotic occlusive disease, AAA is not lipid driven, thus allowing direct evaluation of putative anti-inflammatory effects. The anti-inflammatory potency of increasing doses (0, 20 or 40 mg/day) simvastatin or atorvastatin was evaluated in 63 patients that were at least 6 weeks on statin therapy and who underwent open AAA repair. A comprehensive analysis using immunohistochemistry, mRNA and protein analyses was applied on aortic wall samples collected during surgery. The effect of statins on AAA growth was analyzed in a separate prospective study in incorporating 142 patients. Both statins equally effectively and dose-dependently reduced aortic wall expression of NFkB regulated mediators (i.e. IL-6 (P%26lt;0.001)and MCP-1 (P%26lt;0.001)); shifted macrophage polarization towards a M2 phenotype (P%26lt;0.0003); selectively reduced macrophage-related markers such as cathepsin K and S (P%26lt;0.009 and 0.0027 respectively), and ALOX5 (P%26lt;0.0009), and reduced vascular wall NF kappa B activity (40 mg/day group, P%26lt;0.016). No effect was found on other cell types. Evaluation of the clinical efficacy of statins to reduce AAA progression did not indicate an effect of statins on aneurysm growth (P%26lt;0.337). Hence, in the context of AAA the clinical relevance of statins pleiotropy appears minimal.

• 出版日期2013-1-22