Statins augment collateral growth in response to ischemia but they do not promote cancer and atherosclerosis
Statins augment collateral growth in response to ischemia but they do not promote cancer and atherosclerosis
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DOI：
10.1161/01.hyp.0000126186.29571.41
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发表时间：
2004-06-01
期刊：
影响因子：
8.3
通讯作者：
Nagai, R
中科院分区：
文献类型：
--
作者：
Sata, M;Nishimatsu, H;Nagai, R
3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂，或他汀类药物，被广泛用于降低胆固醇。最近的报道表明，他汀类药物可以促进缺血组织中的血管生成。他汀类药物是否可能增强与肿瘤和动脉粥样硬化相关的不利血管生成仍有待阐明。在这里，我们通过切除右股动脉诱导野生型小鼠的后肢缺血，随后在同一动物中接种癌细胞。西立伐他汀增强了缺血后肢的血流恢复，这是通过激光多普勒成像确定的，而肿瘤的生长显著延缓。西立伐他汀不影响肿瘤毛细血管密度。西立伐他汀、匹伐他汀和氟伐他汀抑制载脂蛋白E缺陷小鼠动脉粥样硬化病变进展，而它们增强缺血后肢的血流恢复和毛细血管形成。低剂量他汀类药物在增加侧支循环恢复和抑制动脉粥样硬化方面比高剂量他汀类药物更有效。这些结果表明，他汀类药物在增加缺血组织侧支血流生长的剂量下可能不会促进癌症和动脉粥样硬化的发展。
3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, or statins, are widely prescribed to lower cholesterol. Recent reports suggest that statins may promote angiogenesis in ischemic tissues. It remains to be elucidated whether statins potentially enhance unfavorable angiogenesis associated with tumor and atherosclerosis. Here, we induced hind limb ischemia in wild-type mice by resecting the right femoral artery and subsequently inoculated cancer cells in the same animal. Cerivastatin enhanced blood flow recovery in the ischemic hind limb as determined by laser Doppler imaging, whereas tumor growth was significantly retarded. Cerivastatin did not affect capillary density in tumors. Cerivastatin, pitavastatin, and fluvastatin inhibited atherosclerotic lesion progression in apolipoprotein E-deficient mice, whereas they augmented blood flow recovery and capillary formation in ischemic hind limb. Low-dose statins were more effective than high-dose statins in both augmentation of collateral flow recovery and inhibition of atherosclerosis. These results suggest that statins may not promote the development of cancer and atherosclerosis at the doses that augment collateral flow growth in ischemic tissues.