Kadoglou N P E, Sailer N, Fotiadis G, Kapelouzou A, Liapis C D
Department of Vascular Surgery, Medical School, University of Athens, Greece.
First Department of Internal Medicine, "Hippokratio" General Hospital of Thessaloniki, Greece.
Exp Clin Endocrinol Diabetes. 2014 Jan;122(1):44-9. doi: 10.1055/s-0033-1358762. Epub 2014 Jan 24.
Novel members of matrix metalloproteinases (MMPs), MMP-7 and MMP-8, have emerged as predictors of cardiovascular events. Our study aimed to evaluate serum MMP-7 and MMP-8 concentrations in patients with type 2 diabetes mellitus (T2DM) and the effects of atorvastatin on them.
We enrolled 85 statin-free subjects with concomitant T2DM and hypercholesterolemia, but without overt micro-/macro-vascular complications (diabetic group - DG). 42 age- and gender-matched healthy subjects without chronic diseases or therapy served as healthy group (HG). All diabetic patients received fix dose of atorvastatin (20 mg/day). Clinical and anthropometrical parameters, lipids, fasting plasma glucose (FPG), serum MMP-7, MMP-8, their inhibitor (TIMP-1), IL-18, hsCRP and insulin resistance (HOMA-IR) were assayed at baseline in all participants and after 3 months in the DG.
At baseline, DG showed higher levels of BMI, systolic blood pressure, insulin resistance and FPG compared to HG (p<0.05). Similarly, DG appeared with elevated concentrations of MMP-7 (4.28±1.01 ng/ml vs 2.63±1.11 ng/ml, p<0.001), MMP-8 (73.07±21.96 ng/ml vs. 21.27±10.49 ng/ml, p<0.001) and inflammatory markers (WBC, hsCRP, IL-18, p<0.010). Importantly, atorvastatin treatment improved lipid profile, significantly reduced the concentrations of MMP-7, MMP-8 and inflammatory markers (p<0.01). Moreover, there was considerable suppression of both MMP-7/TIMP-1 and MMP-8/TIMP-1 ratios (p<0.01). In standard multiple regression analysis, the atorvastatin-induced reduction in MMP-7 was independently associated with LDL and IL-18 downregulation (R(2)=0.648, p=0.017). Similarly, IL-18 changes emerged as an independent determinant of MMP-8 alterations (R(2)=0.678, p=0.007).
Hypercholesterolemic patients with T2DM showed elevated MMP-7 and MMP-8 serum concentrations. Atorvastatin reduced the latter concentrations and their ratio with TIMP-1. Those effects seemed mediated by the atorvastatin-induced suppression of inflammatory mediators. ClinicalTrials.gov Identifier: NCT00636766.
基质金属蛋白酶（MMPs）的新成员MMP - 7和MMP - 8已成为心血管事件的预测指标。我们的研究旨在评估2型糖尿病（T2DM）患者的血清MMP - 7和MMP - 8浓度以及阿托伐他汀对它们的影响。
我们纳入了85例无他汀类药物治疗史、合并T2DM和高胆固醇血症但无明显微血管/大血管并发症的患者（糖尿病组 - DG）。42例年龄和性别匹配、无慢性疾病或未接受治疗的健康受试者作为健康组（HG）。所有糖尿病患者接受固定剂量的阿托伐他汀（20毫克/天）。在所有参与者基线时以及糖尿病组3个月后测定临床和人体测量参数、血脂、空腹血糖（FPG）、血清MMP - 7、MMP - 8、其抑制剂（TIMP - 1）、IL - 18、高敏C反应蛋白（hsCRP）和胰岛素抵抗（HOMA - IR）。
基线时，与健康组相比，糖尿病组的体重指数、收缩压、胰岛素抵抗和空腹血糖水平更高（p<0.05）。同样，糖尿病组的MMP - 7（4.28±1.01纳克/毫升对2.63±1.11纳克/毫升，p<0.001）、MMP - 8（73.07±21.96纳克/毫升对21.27±10.49纳克/毫升，p<0.001）和炎症标志物（白细胞、hsCRP、IL - 18，p<0.010）浓度升高。重要的是，阿托伐他汀治疗改善了血脂谱，显著降低了MMP - 7、MMP - 8和炎症标志物的浓度（p<0.01）。此外，MMP - 7/TIMP - 1和MMP - 8/TIMP - 1比值均受到显著抑制（p<0.01）。在标准多元回归分析中，阿托伐他汀引起的MMP - 7降低与低密度脂蛋白和IL - 18下调独立相关（R² = 0.648，p = 0.017）。同样，IL - 18变化是MMP - 8改变的独立决定因素（R² = 0.678，p = 0.007）。
合并高胆固醇血症的T2DM患者血清MMP - 7和MMP - 8浓度升高。阿托伐他汀降低了后者的浓度及其与TIMP - 1的比值。这些作用似乎是由阿托伐他汀诱导的炎症介质抑制介导的。ClinicalTrials.gov标识符：NCT00636766。
