Effect of intensive lipid-lowering therapy on telomere erosion in endothelial progenitor cells obtained from patients with coronary artery disease
Effect of intensive lipid-lowering therapy on telomere erosion in endothelial progenitor cells obtained from patients with coronary artery disease
复制标题
DOI：
10.1042/cs20080404
复制
发表时间：
2009-06-01
期刊：
影响因子：
6
通讯作者：
Nakamura, Motoyuki
中科院分区：
文献类型：
--
作者：
Satoh, Mamoru;Minami, Yoshitaka;Nakamura, Motoyuki
内皮祖细胞的端粒侵蚀可能是内皮细胞衰老的一个关键因素，并且高度依赖于细胞的氧化损伤。本研究的目的是探讨他汀类药物的降脂治疗是否能减轻冠心病患者的EPC端粒侵蚀。这项研究包括100例稳定期冠心病患者和25例非冠心病患者作为对照。冠心病患者随机接受12个月的强化LLT加阿托伐他汀或中等强度LLT加普伐他汀。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。用荧光原位杂交(FISH)检测EPC端粒长度，用DNA氧化碱基流式细胞术检测DNA氧化损伤。冠心病组EPC端粒长度明显短于对照组，DNA氧化损伤程度明显高于对照组。经过12个月的治疗，强化LLT组的血脂谱变化比中度LLT组更大。强化LLT可显著增加EPC数量，减少DNA氧化损伤(P均<0.05)，端粒长度无明显变化。相反，中度LLT不改变EPC计数或DNA氧化损伤，但显示端粒缩短(P<；0.05)。强化LLT后EPC数量变化与低密度脂蛋白-胆固醇水平呈弱负相关，而中等强度LLT后两者与体外培养的EPC氧化应激无相关性，阿托伐他汀与普伐他汀相比可预防EPC端粒缩短。综上所述，本研究表明，强化LLT可以预防冠心病患者的EPC端粒侵蚀，这可能是强化LLT对这种疾病的有益效果之一。
Telomere erosion of EPCs (endothelial progenitor cells) may be a key factor in endothelial cell senescence and is highly dependent on cellular oxidative damage. The aim of the present study was to investigate whether LLT (lipid-lowering therapy) with statins could attenuate EPC telomere erosion in patients with CAD (coronary artery disease). The study included 100 patients with stable CAD and 25 subjects without CAD as controls. CAD patients were randomized to 12 months of intensive LLT with atorvastatin or moderate LLT with pravastatin. EPCs were obtained from peripheral blood at baseline and after 12 months of statin therapy. Telomere length in EPCs was measured by FISH (fluorescence in situ hybridization) and oxidative DNA damage by flow cytometry of oxidized DNA bases. EPC telomere length was shorter in the CAD group than in the controls, and oxidative DNA damage to EPCs was higher in the CAD group compared with controls. After 12 months of therapy, changes in lipid profiles were greater in the intensive LLT group than in the moderate LLT group. Intensive LLT markedly increased EPC number and decreased oxidative DNA damage in EPCs (both P < 0.05), with no change in telomere length. In contrast, moderate LLT did not change EPC counts or oxidative DNA damage, but showed telomere shortening (P < 0.05). There was a weak negative correlation between changes in EPC number and LDL (low-density lipoprotein)-cholesterol levels after intensive LLT whereas there was no correlation between them after moderate LLT With in vitro culturing of EPCs subjected to oxidative stress, atorvastatin led to the prevention of EPC telomere shortening compared with pravastatin. In conclusion, the present study has demonstrated that intensive LLT may prevent EPC telomere erosion in patients with CAD, possibly contributing to the beneficial effects of intensive LLT in this disorder.