Satoh Mamoru, Minami Yoshitaka, Takahashi Yuji, Tabuchi Tsuyoshi, Itoh Tomonori, Nakamura Motoyuki
Division of Cardiology and Memorial Heart Center, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka 020-8505, Iwate, Japan.
Clin Sci (Lond). 2009 May 1;116(11):827-35. doi: 10.1042/CS20080404.
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.
内皮祖细胞（EPCs）的端粒损耗可能是内皮细胞衰老的关键因素，且高度依赖于细胞氧化损伤。本研究旨在探讨他汀类药物降脂治疗（LLT）是否能减轻冠心病（CAD）患者的EPC端粒损耗。该研究纳入了100例稳定型CAD患者和25例无CAD的受试者作为对照。CAD患者被随机分为接受阿托伐他汀强化LLT治疗12个月组或普伐他汀中度LLT治疗组。在基线时以及他汀治疗12个月后从外周血中获取EPCs。通过荧光原位杂交（FISH）测量EPCs中的端粒长度，并通过氧化DNA碱基的流式细胞术检测氧化DNA损伤。CAD组EPCs的端粒长度比对照组短，且CAD组EPCs的氧化DNA损伤高于对照组。治疗12个月后，强化LLT组的血脂谱变化大于中度LLT组。强化LLT显著增加了EPC数量并降低了EPCs中的氧化DNA损伤（均P<0.05），端粒长度无变化。相比之下，中度LLT未改变EPC计数或氧化DNA损伤，但显示出端粒缩短（P<0.05）。强化LLT后EPC数量变化与低密度脂蛋白（LDL）胆固醇水平之间存在弱负相关，而中度LLT后两者之间无相关性。在体外培养遭受氧化应激的EPCs时，与普伐他汀相比，阿托伐他汀可防止EPC端粒缩短。总之，本研究表明强化LLT可能预防CAD患者的EPC端粒损耗，这可能有助于强化LLT对该疾病的有益作用。
