Leukocyte Telomere Length Is Associated With High-Risk Plaques on Virtual Histology Intravascular Ultrasound and Increased Proinflammatory Activity
Leukocyte Telomere Length Is Associated With High-Risk Plaques on Virtual Histology Intravascular Ultrasound and Increased Proinflammatory Activity
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DOI：
10.1161/atvbaha.111.229237
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发表时间：
2011-09-01
影响因子：
8.7
通讯作者：
Bennett, Martin R.
中科院分区：
文献类型：
--
作者：
Calvert, Patrick A.;Liew, Tze-Vun;Bennett, Martin R.
目的：白细胞端粒长度(LTL)是细胞衰老的标志，与心血管事件呈负相关。方法与结果：170例稳定型心绞痛或急性冠脉综合征患者接受了3支血管内超声虚拟组织学检查，共分析了30372 mm血管内超声回撤和1096个斑块。LTL与斑块体积无关，但与钙化的薄帽纤维斑块(OR1.24；CI1.01~1.53；P=0.039)和总的纤维斑块数目(OR1.19；CI1.02~1.39；P=0.027)相关。冠心病患者单核细胞分泌促炎细胞因子增加。为了模拟白细胞的衰老，我们破坏了端粒与端粒蛋白的结合和表达，保护端粒蛋白-1，诱导DNA损伤。与冠状动脉疾病患者相似，端粒断裂增加单核细胞分泌单核细胞趋化蛋白-1、IL-6和IL-1β和氧化爆发，增加淋巴细胞分泌IL-2和降低淋巴细胞IL-10。结论较短的LTL与虚拟组织学血管内超声的高危斑块形态有关，但与三支血管总斑块负荷无关。端粒破坏的单核细胞表现出更高的促炎活性，这在冠状动脉疾病患者中也可以看到，这表明端粒缩短通过增加促炎活性促进了高危斑块亚型的形成。(动脉血栓血管生物)2011；31：2157-2164。)
Objective-Leukocyte telomere length (LTL), a marker of cellular senescence, is inversely associated with cardiovascular events. However, whether LTL reflects plaque extent or unstable plaques, and the mechanisms underlying any association are unknown.Methods and Results-One hundred seventy patients with stable angina or acute coronary syndrome referred for percutaneous coronary intervention underwent 3-vessel virtual histology intravascular ultrasound; 30 372 mm of intravascular ultrasound pullback and 1096 plaques were analyzed. LTL was not associated with plaque volume but was associated with calcified thin-capped fibroatheroma (OR, 1.24; CI, 1.01-1.53; P = 0.039) and total fibroatheroma numbers (OR, 1.19; CI, 1.02-1.39; P = 0.027). Monocytes from coronary artery disease patients showed increased secretion of proinflammatory cytokines. To mimic leukocyte senescence, we disrupted telomeres and binding and expression of the telomeric protein protection of telomeres protein-1, inducing DNA damage. Telomere disruption increased monocyte secretion of monocyte chemoattractant protein-1, IL-6, and IL-1 beta and oxidative burst, similar to that seen in coronary artery disease patients, and lymphocyte secretion of IL-2 and reduced lymphocyte IL-10.Conclusion-Shorter LTL is associated with high-risk plaque morphology on virtual histology intravascular ultrasound but not total 3-vessel plaque burden. Monocytes with disrupted telomeres show increased proinflammatory activity, which is also seen in coronary artery disease patients, suggesting that telomere shortening promotes high-risk plaque subtypes by increasing proinflammatory activity. (Arterioscler Thromb Vasc Biol. 2011;31:2157-2164.)