Induction of macrophage elastase (MMP-12) gene expression by statins
Induction of macrophage elastase (MMP-12) gene expression by statins
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DOI：
10.1002/jcp.20271
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发表时间：
2005-07-01
影响因子：
5.6
通讯作者：
Mariani, TJ
中科院分区：
文献类型：
--
作者：
Arikan, MC;Shapiro, SD;Mariani, TJ
他汀类药物(包括美伐他汀和洛伐他汀)是一类被广泛处方的降胆固醇药物，其作用是通过抑制3-羟甲基戊二酰辅酶A(HMG CoA)还原酶活性和细胞固醇合成来发挥作用。他汀类药物也因其主要通过直接调节炎症基因表达而抑制炎症的作用而被广泛认识。在此，我们报告他汀类药物还能够增加巨噬细胞弹性蛋白酶(MMP12)的表达。他汀类药物诱导小鼠巨噬细胞中的基质金属蛋白酶-12是HMG辅酶A还原酶抑制所特有的，甲伐他汀类药物可以挽救这种作用，并且在抑制胆固醇生物合成途径的后续步骤后没有观察到这种作用。胆固醇代谢的调节可能导致基质金属蛋白酶-12表达的变化，并在生理和病理生理状态下产生影响。我们得出结论，他汀类药物，除了其先前描述的抗炎特性外，还可能促进激活的巨噬细胞产生一些蛋白水解酶。
The statins (including mevastatin and lovastatin) are a widely prescribed class of serum-cholesterol lowering drugs that function by inhibiting 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase activity and cellular sterol synthesis. Statins are also widely being appreciated for their inhibitory effects upon inflammation, primarily mediated through direct regulation of inflammatory gene expression. Here we report that statins are also capable of increasing the expression of macrophage elastase (MMP-12). The induction of MMP-12 in mouse macrophages by statins is specific for HMG CoA reductase inhibition, rescued by mevalonate and not observed after inhibition of subsequent steps in the cholesterol biosynthetic pathway. Modulation of cholesterol metabolism may lead to changes in MMP-12 expression and subsequent impacts during physiological and pathophysiological states. We conclude that statins, in addition to their previously described anti-inflammatory properties, may promote the production of some proteinases from activated macrophages.