Effect of atorvastatin on microRNA 221/222 expression in endothelial progenitor cells obtained from patients with coronary artery disease
Effect of atorvastatin on microRNA 221/222 expression in endothelial progenitor cells obtained from patients with coronary artery disease
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DOI：
10.1111/j.1365-2362.2009.02110.x
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发表时间：
2009-05-01
影响因子：
5.5
通讯作者：
Nakamura, M.
中科院分区：
文献类型：
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作者：
Minami, Y.;Satoh, M.;Nakamura, M.
内皮祖细胞在维持血管完整性方面发挥着重要作用。他汀类药物的降脂治疗(LLT)可能有助于包括内皮细胞增殖在内的生物学相关活动。MicroRNA(MiR)-221/222是一类新发现的小RNA，其生理作用与内皮细胞的增殖密切相关。因此，我们研究了LLT联合他汀类药物是否会影响从冠心病(CAD)患者获得的内皮祖细胞miR-221/222的表达。这项研究包括44名稳定的CAD患者和22名非CAD患者。冠心病患者随机接受12个月的LLT治疗，分别给予阿托伐他汀(10 mg·d(-1))或普伐他汀(10 mg·d(-1))。从基线和他汀类药物治疗12个月后的外周血中获取内皮祖细胞。实时定量RT-PCR法检测内皮祖细胞miR-221/222的表达水平，冠心病组miR-221/222的表达水平显著高于非冠心病组(P<0.01)。冠心病组miR-221/222水平与EPC数呈弱负相关。治疗12个月后，阿托伐他汀组的血脂变化比普伐他汀组更大。阿托伐他汀能显著增加冠心病患者的EPC数，降低miR-221/222水平(均P<0.05)，而加普伐他汀的LLT对EPC数和miR-221/222水平无明显影响。
Endothelial progenitor cells (EPCs) play an important role in the maintenance of vascular integrity. Lipid lowering therapy (LLT) with statins may contribute to biologically relevant activities including the proliferation of endothelial cells. The physiological role of microRNA (miR)-221/222, a newly discovered class of small RNA, is closely linked to the proliferation of endothelial cells. We therefore investigated whether LLT with statins might affect miR-221/222 expression in EPCs obtained from patients with coronary artery disease (CAD).This study included 44 patients with stable CAD and 22 subjects without CAD (non-CAD). Patients with CAD were randomized to 12 months of LLT with atorvastatin (10 mg day(-1)) or pravastatin (10 mg day(-1)). EPCs were obtained from peripheral blood at baseline and after 12 months of statin therapy. Levels of miR-221/222 in EPCs were measured by real-time RT-PCR.Levels of miR-221/222 were significantly higher in the CAD group than in the non-CAD group (P < 0.01). Levels of miR-221/222 were weakly negatively correlated with EPC number in the CAD group. After 12 months of therapy, changes in lipid profiles were greater in the atorvastatin group than in the pravastatin group. LLT with atorvastatin markedly increased EPC numbers and decreased miR-221/222 levels (all P < 0.05), whereas LLT with pravastatin did not change EPC numbers or miR-221/222 levels.This study demonstrates that LLT with atorvastatin increases EPC numbers and decreases miR-221/222 levels in patients with CAD, possibly contributing to the beneficial effects of LLT with atorvastatin in this disorder.