Vladimirova-Kitova Lyudmila G, Deneva-Koicheva Tania I
Clinic of Cardiology, Medical University Plovdiv, Bulgaria Department of Clinical Laboratory, Medical University Plovdiv, Bulgaria.
Echocardiography. 2011 Feb;28(2):223-34. doi: 10.1111/j.1540-8175.2010.01304.x.
The data on the examination of early vascular alterations in carriers of molecular defects of the low-density lipoprotein-receptor (LDL-R) in comparison to noncarriers with severe hypercholesterolemia are controversial.
To examine the difference between patients with severe hypercholesterolemia, who are carriers and noncarriers of LDL-R defective gene, with respect to their functional (flow-mediated vasodilation) and structural (intima-media thickness of carotid artery) characteristics of arterial wall. A total of 250 hypercholesterolemic patients were enrolled. Biochemistry parameters were examined by routine methods. The molecular biological analysis included-R3500Q-mutation in the Apolipoprotein-B (Apo-B) gene, LDL-R gene mutation and polymorphism (and the promoter region), as large rearrangements. Determination of flow-mediated vasodilation and intima-media thickness of common carotid artery was performed with Hewlett Packard Sonos 5500, using automated computer software MedicaSoft. IMT.lab.
There was no significant difference between the groups with respect to total cholesterol, LDL, HDL, Apo-B, Apolipoprotein A(1) (Apo-A(1) ), asymmetric dimethylarginine (ADMA), homocysteine, and cellular adhesion molecules. The Apo-B/Apo A(1) index differed significantly (t = 11.23, P < 0.001) between the two groups and this difference was found even after adjustment for age and gender. There was no significant difference with respect to the endothelial dependent and independent vasodilatation between the examined groups (P > 0.05). We were founded a significantly higher carotid IMT in the carriers versus noncarriers. This significant difference was confirmed after adjustment for age and gender. Statistically significant correlations we were founded between IMT mean and age (log) (r(xy) = 0.45; P < 0.01), cholesterol × years score (log) (r(xy) = 0.53; P < 0.01), Apo-B/A(1) (log) (r(xy) = 0.66; P < 0.001) in the group of the carriers. Backward selection process selected Apo-B/A(1) as the most important statistically significant factor related to IMT mean of common carotid artery (F = 105.22; P = 0.001; R(2) = 0.72).
Our data demonstrate that carriers of the LDL-R defective gene have a higher carotid IMT and Apo B/Apo A(1) index than noncarriers, whereas no difference between the groups was found with respect to the level of lipid parameters, ADMA, total homocysteine, cell adhesion molecules and %FMD. Apo-B/A(1) is a predictor of IMT mean in the group of the carriers of the LDL-receptor gene.
与患有严重高胆固醇血症的非携带者相比，低密度脂蛋白受体（LDL-R）分子缺陷携带者早期血管改变的检查数据存在争议。
研究严重高胆固醇血症患者中，LDL-R缺陷基因携带者与非携带者在动脉壁功能（血流介导的血管舒张）和结构（颈动脉内膜中层厚度）特征方面的差异。共纳入250例高胆固醇血症患者。通过常规方法检测生化参数。分子生物学分析包括载脂蛋白B（Apo-B）基因中的-R3500Q突变、LDL-R基因突变和多态性（以及启动子区域），以及大片段重排。使用惠普Sonos 5500及自动计算机软件MedicaSoft.IMT.lab测定颈总动脉血流介导的血管舒张和内膜中层厚度。
两组在总胆固醇、低密度脂蛋白、高密度脂蛋白、Apo-B、载脂蛋白A(1)（Apo-A(1)）、不对称二甲基精氨酸（ADMA）、同型半胱氨酸和细胞黏附分子方面无显著差异。两组间Apo-B/Apo A(1)指数差异显著（t = 11.23，P < 0.001），即使在调整年龄和性别后仍存在此差异。所检查的组间在内皮依赖性和非依赖性血管舒张方面无显著差异（P > ）。我们发现携带者的颈动脉内膜中层厚度显著高于非携带者。在调整年龄和性别后，这一显著差异得到证实。在携带者组中，我们发现内膜中层厚度均值与年龄（对数）（r(xy) = 0.45；P < 0.01）、胆固醇×年评分（对数）（r(xy) = 0.53；P < 0.01）、Apo-B/A(1)（对数）（r(xy) = 0.66；P < 0.001）之间存在统计学显著相关性。向后选择过程选择Apo-B/A(1)作为与颈总动脉内膜中层厚度均值相关的最重要统计学显著因素（F = 105.22；P = 0.001；R(2) = 0.72）。
我们的数据表明，LDL-R缺陷基因携带者的颈动脉内膜中层厚度和Apo B/Apo A(1)指数高于非携带者，而两组在脂质参数水平、ADMA、总同型半胱氨酸、细胞黏附分子和血流介导的血管舒张百分比方面无差异。Apo-B/A(1)是LDL受体基因携带者组内膜中层厚度均值的预测指标。
