University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
PLoS One. 2011 Jan 25;6(1):e16413. doi: 10.1371/journal.pone.0016413.
Recent clinical trials suggest an LDL-independent superiority of intensive statin therapy in reducing target vessel revascularization and peri-procedural myocardial infarctions in patients who undergo percutaneous coronary interventions (PCI). While animal studies demonstrate that statins mobilize endothelial progenitor cells (EPCs) which can enhance arterial repair and attenuate neointimal formation, the precise explanation for the clinical PCI benefits of high dose statin therapy remain elusive. Thus we serially assessed patients undergoing PCI to test the hypothesis that high dose Atorvastatin therapy initiated prior to PCI mobilizes EPCs that may be capable of enhancing arterial repair.
Statin naïve male patients undergoing angiography for stent placement were randomized to standard therapy without Atorvastatin (n = 10) or treatment with Atorvastatin 80 mg (n = 10) beginning three days prior to stent implantation. EPCs were defined by flow cytometry (e.g., surface marker profile of CD45dim/34+/133+/117+). As well, we also enumerated cultured angiogenic cells (CACs) by standard in vitro culture assay. While EPC levels did not fluctuate over time for the patients free of Atorvastatin, there was a 3.5-fold increase in EPC levels with high dose Atorvastatin beginning within 3 days of the first dose (and immediately pre-PCI) which persisted at 4 and 24 hours post-PCI (p<0.05). There was a similar rise in CAC levels as assessed by in vitro culture. CACs cultured in the presence of Atorvastatin failed to show augmented survival or VEGF secretion but displayed a 2-fold increase in adhesion to stent struts (p<0.05).
High dose Atorvastatin therapy pre-PCI improves EPC number and CAC number and function in humans which may in part explain the benefit in clinical outcomes seen in patients undergoing coronary interventions.
最近的临床试验表明，与标准强度他汀类药物治疗相比，强化他汀类药物治疗可降低经皮冠状动脉介入治疗（PCI）患者的靶血管血运重建和围手术期心肌梗死发生率。虽然动物研究表明他汀类药物可动员内皮祖细胞（EPC），从而增强动脉修复并减轻新生内膜形成，但他汀类药物高剂量治疗对 PCI 临床获益的确切解释仍不清楚。因此，我们连续评估了接受 PCI 的患者，以检验如下假说，即在 PCI 前开始高剂量阿托伐他汀治疗可动员 EPC，从而增强动脉修复。
纳入接受血管造影以植入支架的他汀类药物初治男性患者，随机分为标准治疗组（无阿托伐他汀，n = 10）或阿托伐他汀 80 mg 治疗组（阿托伐他汀治疗，n = 10，于支架植入前 3 天开始）。EPC 通过流式细胞术（例如，CD45dim/34+/133+/117+表面标志物特征）进行定义。此外，我们还通过标准体外培养测定法对培养的血管生成细胞（CAC）进行计数。尽管无阿托伐他汀的患者 EPC 水平随时间无波动，但高剂量阿托伐他汀治疗开始后 3 天内（并在 PCI 前即刻）EPC 水平增加了 3.5 倍，PCI 后 4 小时和 24 小时仍保持升高（p<0.05）。通过体外培养检测到 CAC 水平也有类似升高。在阿托伐他汀存在的情况下培养的 CAC 未能显示出增强的存活或 VEGF 分泌，但对支架支柱的粘附增加了 2 倍（p<0.05）。
PCI 前高剂量阿托伐他汀治疗可提高人类 EPC 数量和 CAC 数量及功能，这可能部分解释了接受冠状动脉介入治疗的患者临床结局获益的原因。
