Baumann Marcus, Richart Tom, Sollinger Daniel, Pelisek Jaroslav, Roos Marcel, Kouznetsova Tatiana, Eckstein Hans-Henning, Heemann Uwe, Staessen Jan A
Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Cardiovasc Diabetol. 2009 Aug 6;8:45. doi: 10.1186/1475-2840-8-45.
Nepsilon-carboxymethyllysine (CML) is the major non-cross linking advanced glycation end product (AGE). CML is elevated in diabetic patients and apparent in atherosclerotic lesions. AGEs are associated with hypertension and arterial stiffness potentially by qualitative changes of elastic fibers. We investigated whether CML affects carotid and aortic properties in normoglycemic subjects.
Hundred-two subjects (age 48.2+/-11.3 years) of the FLEMENGHO study were stratified according to the median of the plasma CML level (200.8 ng/ml; 25th percentile: 181.6 ng/ml, 75th percentile: 226.1 ng/ml) into "high CML" versus "low CML" as determined by ELISA. Local carotid artery properties, carotid intima media thickness (IMT), aortic pulse wave velocity (PWV), blood pressure and fetuin-A were analyzed. In 26 patients after carotidectomy, CML was visualized using immunohistochemistry.
According to the CML median, groups were similar for anthropometric and biochemical data. Carotid diameter was enlarged in the "high" CML group (485.7+/-122.2 versus 421.2+/-133.2 microm; P<0.05), in particular in participants with elevated blood pressure and with "high" CML ("low" CML: 377.9+/-122.2 microm and "high" CML: 514.5+/-151.6 microm; P<0.001). CML was associated fetuin-A as marker of vascular inflammation in the whole cohort (r=0.28; P<0.01) and with carotid diameter in hypertensive subjects (r=0.42; P<0.01). CML level had no effect on aortic stiffness. CML was detected in the subendothelial space of human carotid arteries.
In normoglycemic subjects CML was associated with carotid diameter without adaptive changes of elastic properties and with fetuin-A as vascular inflammation marker, in particular in subjects with elevated blood pressure. This may suggest qualitative changes of elastic fibers resulting in a defective mechanotransduction, in particular as CML is present in human carotid arteries.
N-ε-羧甲基赖氨酸（CML）是主要的非交联晚期糖基化终产物（AGE）。糖尿病患者体内CML水平升高，且在动脉粥样硬化病变中较为明显。AGEs可能通过弹性纤维的质性改变与高血压和动脉僵硬度相关。我们研究了CML是否会影响血糖正常受试者的颈动脉和主动脉特性。
根据FLEMENGHO研究中102名受试者（年龄48.2±11.3岁）血浆CML水平的中位数（200.8 ng/ml；第25百分位数：181.6 ng/ml，第75百分位数：226.1 ng/ml），通过酶联免疫吸附测定法（ELISA）将其分为“高CML组”和“低CML组”。分析局部颈动脉特性、颈动脉内膜中层厚度（IMT）、主动脉脉搏波速度（PWV）、血压和胎球蛋白-A。对26例颈动脉切除术后的患者，采用免疫组织化学方法观察CML。
根据CML中位数，两组在人体测量和生化数据方面相似。“高”CML组的颈动脉直径增大（485.7±122.2对421.2±133.2微米；P<0.05），特别是在血压升高且CML“高”的参与者中（“低”CML：377.9±122.2微米，“高”CML：514.5±151.6微米；P<0.001）。在整个队列中，CML与作为血管炎症标志物的胎球蛋白-A相关（r=0.28；P<0.01），在高血压受试者中与颈动脉直径相关（r=0.42；P<0.01）。CML水平对主动脉僵硬度无影响。在人颈动脉的内皮下空间检测到CML。
在血糖正常的受试者中，CML与颈动脉直径相关，弹性特性无适应性变化，且与作为血管炎症标志物的胎球蛋白-A相关，特别是在血压升高的受试者中。这可能提示弹性纤维的质性改变导致机械转导缺陷，尤其是因为CML存在于人体颈动脉中。
