Departments of Clinical Sciences Malmö, Malmö University Hospital, Malmö, Sweden.
Circ Res. 2010 Apr 2;106(6):1174-7. doi: 10.1161/CIRCRESAHA.109.211201. Epub 2010 Feb 18.
Atherosclerotic plaques that give rise to acute clinical symptoms are typically characterized by degradation of the connective tissue and plaque rupture. Experimental studies have shown that mechanisms to repair vulnerable lesions exist, but the rate of remodeling of human plaque tissue has not been studied.
In the present study, we determined the biological age of different components of advanced human atherosclerotic plaques by analyzing tissue levels of (14)C released into the atmosphere during the nuclear weapons tests in the late 1950s and early 1960s.
Atherosclerotic plaques were obtained from 10 patients (age 46 to 80 years) undergoing carotid surgery. Different regions of the plaques were dissected and analyzed for (14)C content using accelerator mass spectrometry. At the time of surgery, the mean biological age of the cap region was 6.4+/-3.2 years, which was significantly lower than that of the shoulder region (12.9+/-3.0 years, P<0.01), the interface toward the media (12.4+/-3.3 years, P<0.01), and the core (9.8+/-4.5 years, P<0.05). Analysis of proliferative activity and rate of apoptosis showed no signs of increased cellular turnover in the cap, suggesting that the lower (14)C content reflected a more recent time of formation.
These results show that the turnover time of human plaque tissue is very long and may explain why regression of atherosclerotic plaque size rarely is observed in cardiovascular intervention trials.
导致急性临床症状的动脉粥样硬化斑块通常表现为细胞外基质的降解和斑块破裂。实验研究表明,存在修复易损病变的机制,但尚未研究人类斑块组织的重塑率。
本研究通过分析上世纪 50 年代末和 60 年代核试验期间释放到大气中的(14)C 组织水平,确定了晚期人类动脉粥样硬化斑块不同成分的生物年龄。
从 10 名(年龄 46 至 80 岁)接受颈动脉手术的患者中获取动脉粥样硬化斑块。使用加速器质谱法对斑块的不同区域进行(14)C 含量分析。在手术时,帽状区域的平均生物年龄为 6.4+/-3.2 岁,明显低于肩部区域(12.9+/-3.0 岁,P<0.01)、朝向中膜的界面(12.4+/-3.3 岁,P<0.01)和核心(9.8+/-4.5 岁,P<0.05)。增殖活性和细胞凋亡率分析显示,帽状区域没有细胞更新增加的迹象,这表明较低的(14)C 含量反映了形成的较新时间。
这些结果表明,人类斑块组织的更新时间非常长,这可能解释了为什么在心血管介入试验中很少观察到动脉粥样硬化斑块大小的消退。