Li Fangming, Guo Yi, Jiang Xin, Zhong Jianxin, Li Guandong, Sun Shenggang
Department of Neurology, Jiangmen Central Hospital, Jiangmen, Guangdong 529070;
Exp Ther Med. 2013 Jul;6(1):204-208. doi: 10.3892/etm.2013.1082. Epub 2013 Apr 29.
The activation of telomerase in unstable plaques is an important factor in atherosclerosis, and may be predictive of the risk of cerebrovascular diseases. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activation. The aim of the present study was to investigate whether aspirin inhibits the activation of telomerase and hTERT in unstable carotid plaques. Polymorphonuclear neutrophils (PMNs) derived from carotid plaques were isolated from the washing medium of angioplasty balloons, while circulating PMNs, isolated from arterial blood, served as the controls. A polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) enzyme-linked immunosorbent assay (ELISA) was used to measure the telomerase activity in the cells following treatment with aspirin. The mRNA and protein expression of hTERT were detected by a reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis, respectively. The results revealed that the atherosclerotic plaques were positive for telomerase activity, and that aspirin inhibited the telomerase activity of the PMNs derived from the plaques. In addition, aspirin was demonstrated to inhibit the mRNA and protein expression of hTERT through the suppression of hTERT transcriptional activity; however, it had no inhibitory effect on the telomerase activity of the circulating PMNs. Thus, the activation of telomerase in resident PMNs is critical in the instability of carotid plaques. The upregulation of telomerase and hTERT during the progression of atherosclerosis may indicate a role for telomerase in the vascular remodeling that occurs during atherogenesis. Aspirin was demonstrated to inhibit the activation of telomerase via an hTERT-dependent manner in the PMN cells of unstable carotid plaques, and thus hTERT may be considered as a target in the treatment of cerebrovascular diseases.
端粒酶在不稳定斑块中的激活是动脉粥样硬化的一个重要因素，可能预示着脑血管疾病的风险。人端粒酶逆转录酶（hTERT）是端粒酶的一个亚基，对端粒酶的激活至关重要。本研究的目的是探讨阿司匹林是否能抑制不稳定颈动脉斑块中端粒酶和hTERT的激活。从血管成形术球囊的冲洗液中分离出颈动脉斑块来源的多形核中性粒细胞（PMN），而从动脉血中分离出的循环PMN作为对照。采用基于聚合酶链反应的端粒重复序列扩增协议（TRAP）酶联免疫吸附测定（ELISA）来测量用阿司匹林处理后细胞中的端粒酶活性。分别通过逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹分析检测hTERT的mRNA和蛋白表达。结果显示，动脉粥样硬化斑块的端粒酶活性呈阳性，且阿司匹林抑制了斑块来源的PMN的端粒酶活性。此外，阿司匹林通过抑制hTERT转录活性来抑制hTERT的mRNA和蛋白表达；然而，它对循环PMN的端粒酶活性没有抑制作用。因此，驻留PMN中端粒酶的激活在颈动脉斑块的不稳定性中起关键作用。动脉粥样硬化进展过程中端粒酶和hTERT的上调可能表明端粒酶在动脉粥样硬化发生过程中的血管重塑中发挥作用。阿司匹林在不稳定颈动脉斑块的PMN细胞中通过依赖hTERT的方式抑制端粒酶的激活，因此hTERT可被视为脑血管疾病治疗的一个靶点。
