Acarbose treatments improve arterial stiffness in patients with type 2 diabetes mellitus

Aims/Introduction: Although the improvement of postprandial hyperglycemia by an alpha‐glucosidase inhibitor (α‐GI) has been associated with a risk reduction of cardiovascular events, the relationship between postprandial hyperglycemia and arterial stiffness has not been well understood. We therefore examined whether ameliorating the postprandial state by α‐GI leads to an improvement in arterial stiffness. Materials and Methods: A total of 22 patients with type 2 diabetes mellitus were treated with acarbose. Cardio‐ankle vascular index (CAVI) as the arterial stiffness was measured by using a VaSera CAVI instrument before and 12 months after acarbose treatment. Serum high‐sensitivity C‐reactive protein (hs‐CRP), pentraxin‐3 (PTX3) and matrix metalloproteinase (MMP) ‐2, ‐9 were measured at the same time points. Furthermore, circulating peripheral blood mononuclear cells were examined for the frequencies of CD14 positive cells expressing membrane type‐1 MMP (MT1‐MMP) at the single cell level using flow cytometry. Results: After acarbose treatment, postprandial glucose and glycosylated hemoglobin (HbA_1c) were significantly decreased. Serum levels of hs‐CRP, PTX3, MMP‐2 and MMP‐9 were significantly decreased. CAVI showed a significant reduction, although the changes were not significant in blood pressure and heart rate. MT1‐MMP expression was significantly decreased by acarbose treatment. In multivariate analysis, improvement of blood glucose, decrease of PTX3 levels and MT1‐MMP expression were independent predictors of beneficial change in CAVI. Conclusions: The present study showed that the beneficial effects of acarbose on arterial stiffness are mediated by an improvement of postprandial hyperglycemia and vascular remodeling markers. In conclusion, acarbose treatment might reduce the risk of cardiovascular diseases by altering the arterial stiffness in postprandial hyperglycemic status. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00079.x , 2010)     

Matrix Metalloproteinase‐2 and ‐9 Levels in Patients with Dilated Ascending Aorta and Bicuspid Aortic Valve

Background: Predictors of aortic dilatation are not well‐described in patients with bicuspid aortic valve (BAV). Changes in extracellular matrix composition in the aortic wall may play an important role. Our study aimed to examine the relationship between ascending aortic dilatation and biochemical markers for collagen metabolism, such as matrix metalloproteinase‐2 (MMP‐2) and matrix metalloproteinase‐9 (MMP‐9) levels in patients with BAV. Methods: All patients underwent cardiac echocardiography using a standard protocol, and aortic measurements were made in end‐diastole. One hundred twelve BAV patients with no or mild valvular impairment were recruited and grouped according to the aortic dimensions corrected for body surface area (BSA) and age. There were 54 patients with dilated ascending aorta (Group 1) and 58 patients with nondilated ascending aorta (group 2). The plasma levels of MMP‐2 and MMP‐9 were determined by ELISA. Results: The mean ascending aorta diameter was 4.49 ± 0.49 mm in group 1 and 3.51 ± 0.46 mm in group 2 (P < 0.001). There were no significant difference in gender, BSA, presence of hypertension, diabetes mellitus, hyperlipidemia, and smoking between the 2 groups. Nevertheless, no significant difference was observed in the levels of MMP‐2 and MMP‐9 between the 2 groups. The ascending aorta diameter correlated significantly with age (r = 0.438 P < 0.001). No significant correlation was observed between plasma MMP‐2 and MMP‐9 concentration and ascending aorta diameter, respectively (r = ?0.005 P = 0.58, r = ?0.106 P = 0.07). Multivariate analysis showed that age was independent predictor of aortic dilatation (P ≤ 0.001). Conclusion: Age was an independent predictor of aortic dilatation in patients with BAV, whereas MMP‐2 and 9 levels were not relevant by aortic dilatation.     

Plasma matrix metalloproteinase 7, CC-chemokine ligand 18, and periostin as markers for pulmonary sarcoidosis

BackgroundSome patients with sarcoidosis experience worsening of pulmonary lesions. However, no biomarker has been identified that reflects pulmonary disease status in sarcoidosis. We investigated the usefulness of potential markers of pulmonary fibrosis in patients with sarcoidosis.MethodsPlasma matrix metalloproteinase 7 (MMP-7), CC-chemokine ligand 18 (CCL-18), and periostin levels were evaluated in 60 patients with sarcoidosis and 30 healthy controls; bronchoalveolar lavage fluid levels were analyzed in 22 patients with sarcoidosis. To determine the usefulness of these markers, we explored potential correlations between these markers and sarcoidosis clinical characteristics.ResultsPlasma MMP-7, CCL-18, and periostin concentrations were significantly higher in patients with sarcoidosis than those in healthy controls. MMP-7 concentrations in plasma and bronchoalveolar lavage fluid were higher in patients with sarcoidosis with parenchymal infiltration than in those without lung lesions. Moreover, MMP-7 concentration was negatively correlated with pulmonary function.ConclusionAmong these novel biomarkers, MMP-7 most precisely reflected pulmonary sarcoidosis disease status and thus, might be useful for diagnosing and evaluating sarcoidosis, particularly in patients with pulmonary parenchymal lesions.     

不同调脂方案对冠心病患者基质金属蛋白酶的影响

Objective Patients with coronary artery disease (CAD, stenosis between 50%-70% evidenced by coronary angiography) were treated with atorvastatin 40 mg(n = 19) or atorvastatin 10 mg in combination with ezetimibe 10 mg (n = 23). Blood lipid profile and metal]oproteinases were monitored up to 3 months. Methods Cholesterol (TC) , triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), liver function, renal function, creatine kinase, MMP-2, MMP-9, TIMP-1 were measured at baseline and at 1 month and 3 months post therapy. Results (1) At 3 months, LDL-C was similarly reduced in monotherapy group[(1.94±0.49) mmol/L, 37.82% reduction compared to baseline] and in combined therapy group [(1.92±0.54) mmol/L, 38. 26% reduction compared to baseline]. (2) AST, ALT, renal function and creatine kinase remained unchanged post various therapy (all P ＞ 0.05). (3) MMP-2, MMP-9 significantly decreased and TIMP-1 significantly increased at 3 months compared to baseline in monotherapy group but these parameters remained unchanged in combined therapy group. Conclusion Both therapy regimens were well tolerated and similarly effectively reduced blood lipids and 40 mg atorvastatin monotherapy regimen is superior to atorvastatin 10 mg plus ezetimibe10 mg regimen in improving metalloproteinases parameters.     

经皮冠状动脉介入治疗后肌钙蛋白I阳性患者血清基质金属蛋白酶水平升高的临床意义

目的 :探讨血清基质金属蛋白酶 (MMP)在稳定型心绞痛患者中介入治疗后的表达。方法 :16例冠状动脉造影正常的患者 (对照组 )及 5 1例行冠状动脉介入治疗的稳定型心绞痛患者 (患者组 )入选 ;术后常规查肌钙蛋白I(cTnI) ,分别采取术前 ,术后第 1、第 3及第 5天的外周血 ,Elisa试剂盒测定MMP 2、MMP 9的水平。结果 :5 1例患者中共有 2 1例患者cTnI增高 ,平均 (0 .6 8± 0 .2 3) μg/L ;术前两组的MMP水平无明显差异 ;cTnI阳性者的MMP 9在术后第 1天明显高于阴性者及对照组〔(198± 5 8.5 )∶(14 4± 4 8.3)、(132± 4 6 .7) μg/L ,均 P <0 .0 5〕 ,并在术后第 3天、第 5天保持较高水平 ;MMP 2仅在术后第 1天增高 ,第 3天、第 5天恢复正常。结论 :冠状动脉介入治疗后心肌微损伤的发生率较高 ,这种心肌微损伤对患者的预后有一定的影响 ;血清MMP水平的增高 ,可能是此类患者临床预后较差的原因之一。     

间质金属蛋白酶基因多态性与中心性肥胖在非酒精性脂肪肝病中交互作用研究

目的 探讨间质金属蛋白酶-9(MMP-9)-1562C/T(rs3918242)以及MMP-2-1306C/T(rs243865)位点单核苷酸多态性(SNP)与非酒精性脂肪肝(NAFLD)遗传易感性以及与中心性肥胖交互作用。方法 对545例NAFLD患者和636例正常对照,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析rs24386以及rs3918242基因型、非条件logistic分析各基因型与脂肪肝发病易感性关系,利用非条件logistic分析和广义多因子降维(GMDR)法分析rs3918242、rs243865与中心性肥胖的交互作用。结果 MMP-9 rs3918242位点T基因携带者(TT/CT)与非T基因携带者(CC)的NAFLD罹患风险明显增加(OR=1.67,95%CI:1.32～2.12,P=0.001;调整OR=1.65,95%CI:1.31～2.01,P=0.008);而MMP-2 rs243865位点T基因携带者(TT/CT)与非T基因携带者(CC)的NAFLD罹患风险明显降低(OR=0.68,95%CI:0.53～0.86,P=0.001;调整OR=0.66,95%CI:0.49～0.90,P=0.007)。广义多因子降维法分析结果显示,rs3918242与中心性肥胖在NAFLD发病中存在交互作用(P=0.001)。利用非条件logistic校正年龄、性别、腰围、BMI、LDL-C、HDL-C、FPG、胰岛素抵抗指数后,分析显示,携带rs3918242 TT/CT基因型中心性肥胖个体罹患NAFLD的风险高于携带CC基因非吸烟个体(OR=4.50,95%CI:2.78～7.17,P=0.007)。结论 MMP-9基因的rs3918242以及MMP-2基因的rs243865与NAFLD患病罹患风险紧密相关,rs3918242与中心性肥胖在NAFLD发病中具有协同效应。     

基质金属蛋白酶/组织金属蛋白酶抑制物表达失衡在大鼠肾脏衰老过程中的意义

目的:探讨基质金属蛋白酶(MMPs)及其抑制物(TIMPs)在大鼠肾脏衰老过程中的作用。方法:选用3、12和24月龄大鼠，采用免疫组化技术分别检测基质金属蛋白酶—2、9(MMP—2、9)、组织金属蛋白酶抑制物—1、2(TIMP—1、2)、转化生长因子—β1(TGF—β1)等在不同月龄大鼠肾组织中的表达。结果TIMP—1、TIMP—2及TGF—β1主要表达在肾小球、肾小管、间质及血管，并随增龄表达增强(P＜O．01)；MMP—9、MMP—2主要表达在肾小管上皮细胞，随增龄表达无变化；TIMP—1与TGF—β1与肾小球硬化面积有相关性(r分别为O．751、O．771，P＜O．05)；TIMP—1与TIMP—2与小管间质纤维化面积有相关性(r分别为O．783、O．766，P＜O．O5)。结论:MMPs／TIMPs表达失衡在肾脏衰老过程中可能起重要作用。     

CD147分子和基质金属蛋白酶在类风湿关节炎滑膜中的表达

目的 探讨类风湿关节炎(RA)滑膜组织CD147的表达及其与基质金属蛋白酶(MMP)-01和MMP-2表达的相关性。方法 采用免疫组织化学SP(streptavidin／peroxidase)染色方法检测11例RA患者受损关节软骨-血管翳接合部（CPJ)滑膜组织中CD147和MMP-1及MMP-2的表达，并与3例骨关节炎（OA)患者滑膜组织CD147和MMP-1及MMP-2的检测相对照。结果 3例OA滑膜组织CD147和MMP-1及MMP-2的表达均为阴性，而11例RA滑膜组织中均有CD147和MMP-1及MMP-2的表达。其中，表达CD147的细胞为单核-巨噬细胞、淋巴细胞和滑膜成纤维样细胞，表达MMP-1及MMP-2的细胞为滑膜成纤维样细胞。统计学分析表明RA滑膜细胞CD147的表达和MMP-1及MMP-2的表达间存在显著相关性。结论 CD147在RA滑膜组织中表达增高，可能是导敏RA受损关节软骨、骨基质降解的重要因素之一。     

左向右分流型先天性心脏病患儿血清MMP-2和MMP-9变化

目的探讨左向右分流先天性心脏病（CHD）患儿血清基质金属蛋白酶（MMPs）-2、9水平的变化及意义。方法采用ELISA方法检测并比较40例CHD患儿（其中无肺动脉高压组22例、肺动脉高压组18例）和20例健康患儿的血清MMP-2、MMP～9。结果CHD无肺动脉高压组及肺动脉高压组患儿MMP-2（分别为206．14±20．62及258．83±31．44,pg／ml）、MMP-9（分别为207．68±20．77及240．00±31．10pg／m1）与正常对照组相比均有显著性（P均小于0．05）;而肺动脉高压组MMP-2及MMP-9水平明显高于无肺动脉高压组,差异有显著性（P均小于0．01）。CHD患儿血清MMP-2、MMP-9与LVEF、LVFs均无明显相关性（P〉0．05）;CHD患儿血清MMP-2及MMP-9浓度与肺动脉收缩压呈正相关（r分别为0．783及0．635,n=40,P〈0．05）。结论CHD肺动脉高压患儿血清MMP-2、MMP-9浓度升高并与肺动脉收缩压成正相关,提示MMP-2、MMP-9与肺动脉高压的病理生理有关。