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健康受试者、糖尿病患者及急性冠状动脉综合征患者中金属蛋白酶-2和-9的比较。

Comparison between metalloproteinases-2 and -9 in healthy subjects, diabetics, and subjects with acute coronary syndrome.

作者信息

Derosa Giuseppe, D'Angelo Angela, Scalise Filippo, Avanzini Maria A, Tinelli Carmine, Peros Emmanouil, Fogari Elena, Cicero Arrigo F G

机构信息

Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S Matteo, Pavia, Italy.

出版信息

Heart Vessels. 2007 Nov;22(6):361-70. doi: 10.1007/s00380-007-0989-6. Epub 2007 Nov 26.

Abstract

We hypothesized that matrix metalloproteinase (MMP)-2, -9, and tissue inhibitor metalloproteinase-1, -2 (TIMP-1, -2) would be abnormal in diabetes and in acute coronary syndromes (ACS). We measured MMP-2, -9, and TIMP-1, -2 plasma levels in healthy subjects (controls), in type 2 diabetic patients, in nondiabetic patients with ACS (ACS) and in diabetic patients with ACS (DACS). We enrolled 165 controls, 181 diabetic patients, 78 ACS, and 46 DACS. We measured also BMI (body mass index), HbA(1c) (glycated hemoglobin) FPG (fasting plasma glucosa), FPI (fasting plasma insulin), HOMA index (homeostasis model assessment index), SBP (systolic blood pressure), DBP (diastolic blood pressure), TC (total cholesterol), LDL-C (low density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), Tg (triglycerides), Lp(a) (lipoprotein(a)) PAI-1 (plasminogen activator inhibitor-1), Hct (homocysteine), Fg (fibrinogen), and hs-CRP (high-sensitivity C-reactive protein). A significant increase of BMI was observed in the diabetic group, in ACS and DACS patients compared to controls. A significant increase of SBP and DBP resulted in the diabetic and DACS groups, while only SBP improvement was present in ACS patients with respect to controls. A decrease in SBP and DBP was observed in the ACS group, while SBP variation was present in DACS patients compared to diabetics, and DBP increase was obtained in the DACS group with respect to ACS patients. TC, LDL-C, Tg, and Lp(a) increase was present in diabetics, while TC, Tg, and Lp(a) improvement was present in ACS and DACS patients with a significant decrease of HDL-C levels in diabetic, ACS, and DACS groups compared to controls. A decrease in LDL-C was obtained in ACS and DACS groups, while HDL-C increase was observed in these patients with respect to diabetics. Tg levels were higher in the DACS group compared to diabetics and ACS patients, respectively. Increases in PAI-1, Hct, Fg, and hs-CRP were present in diabetic and DACS groups, while PAI-1, Hct, and hs-CRP improvement was obtained in ACS patients with respect to controls. Higher PAI-1 levels came about in ACS and DACS groups, while HCT and Fg levels were lower in ACS patients compared to diabetics. An increase in Fg was present in the DACS group with respect to ACS patients. A decrease in Hs-CRP was observed in DACS patients compared to diabetics and the ACS group, respectively. Higher MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were present in diabetic, ACS, and DACS patients compared to controls. Significant MMP-2, TIMP-1, and TIMP-2 increases were observed in ACS and DACS groups, while MMP-9 decreased in these patients compared to diabetics. In conclusion, MMP-2, MMP-9, TIMP-1, and TIMP-2 plasma levels were higher in diabetic, ACS, and DACS patients, which may reflect abnormal extracellular matrix metabolism in diabetes and in acute coronary syndrome.

摘要

我们推测基质金属蛋白酶(MMP)-2、-9以及组织金属蛋白酶抑制剂-1、-2(TIMP-1、-2)在糖尿病和急性冠脉综合征(ACS)中会出现异常。我们测定了健康受试者(对照组)、2型糖尿病患者、非糖尿病ACS患者(ACS组)以及糖尿病合并ACS患者(DACS组)血浆中MMP-2、-9以及TIMP-1、-2的水平。我们招募了165名对照组受试者、181名糖尿病患者、78名ACS患者以及46名DACS患者。我们还测量了体重指数(BMI)、糖化血红蛋白(HbA1c)、空腹血糖(FPG)、空腹血浆胰岛素(FPI)、稳态模型评估指数(HOMA指数)、收缩压(SBP)、舒张压(DBP)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(Tg)、脂蛋白(a)[Lp(a)]、纤溶酶原激活物抑制剂-1(PAI-1)、同型半胱氨酸(Hct)、纤维蛋白原(Fg)以及高敏C反应蛋白(hs-CRP)。与对照组相比,糖尿病组、ACS组和DACS组患者的BMI显著升高。糖尿病组和DACS组患者的SBP和DBP显著升高,而ACS组患者仅SBP较对照组有所改善。ACS组患者的SBP和DBP降低,而DACS组患者与糖尿病患者相比SBP有变化,且DACS组患者与ACS组患者相比DBP升高。糖尿病患者的TC、LDL-C、Tg和Lp(a)升高,而ACS组和DACS组患者的TC、Tg和Lp(a)有所改善,糖尿病组、ACS组和DACS组患者的HDL-C水平相较于对照组显著降低。ACS组和DACS组患者的LDL-C降低,而这两组患者与糖尿病患者相比HDL-C升高。DACS组患者的Tg水平分别高于糖尿病患者和ACS组患者。糖尿病组和DACS组患者的PAI-1、Hct,Fg和hs-CRP升高,而ACS组患者与对照组相比PAI-1、Hct和hs-CRP有所改善。ACS组和DACS组患者的PAI-1水平较高,而ACS组患者与糖尿病患者相比HCT和Fg水平较低。DACS组患者与ACS组患者相比Fg升高。DACS组患者与糖尿病患者及ACS组相比hs-CRP降低。与对照组相比,糖尿病组、ACS组和DACS组患者的MMP-2、MMP-9、TIMP-1和TIMP-2水平较高。ACS组和DACS组患者的MMP-2、TIMP-1和TIMP-2显著升高,而这两组患者与糖尿病患者相比MMP-9降低。总之,糖尿病组、ACS组和DACS组患者血浆中MMP-2、MMP-9、TIMP-1和TIMP-2水平较高,这可能反映了糖尿病和急性冠脉综合征中细胞外基质代谢异常。

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