Efeitos dos níveis de MMP-2 e TIMP-2 e dos polimorfismos da MMP-2-1575 G/A; -1306 C/T e -735 C/T na hipertensão resistente = Effects of MMP-2 and TIMP-2 levels and -1575 G/A; -1306 C/T and -735 C/T MMP-2 polymorphisms in resistant hypertension
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Osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) are critical regulators of bone remodeling and RANKL/RANK signaling could also play an important role in the remodeling process of several tissues, such as myocardium. Therefore, we investigated whether the serum concentrations of OPG and RANKL correlate with the serum levels of metalloproteinase-1 (MMP-1), MMP-9 and tissue inhibitors of MMP-1 (TIMP-1), which are known regulators of myocardial healing in acute myocardial infarction (AMI) patients.We analyzed blood samples from 51 consecutively hospitalized men with AMI, 12 men with established ischemic heart failure (New York Heart Association category II, NYHA-II) and 12 healthy men age-matched to the NYHA-II patients. Serum levels of MMP-1, MMP-9, TIMP-1, OPG and RANKL were quantified using commercially available ELISA kits. AMI patients were sampled 4 days and 6 months after MI.Our data revealed increased serum levels of OPG, RANKL, MMP-1 and TIMP-1 levels and significant correlations between increased RANKL levels and MMP-1 and TIMP-1 serum levels 6 months after MI. In addition, the ratio OPG/RANKL was very low 6 months after MI, suggesting that the nuclear factor kappa-B signaling is possibly more active 6 months post-MI than it is on day 4 post-MI.Our data suggest that OPG, RANKL, MMP-1 and TIMP-1 serum levels can be potential mediators of myocardial healing after MI. However, further large studies are needed to confirm the utility of OPG and RANKL as markers of healing after ST elevation in MI.
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Gestational hypertension
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Matrix metalloproteinase (MMP) -2 C-735 T and MMP-7 A-181 G genotypes were studied in 144 pregnant patients with mild and severe preeclampsia and 103 healthy pregnant women. Significantly higher frequencies of CT and TT genotypes in patients compared to controls increased the risk of preeclampsia by 2.42 and 3.13 times, respectively. In severe preeclamptic women in the presence of MMP-2 CT the level of total antioxidant capacity was significantly lower than MMP-2 CC genotype. Also, in the presence of MMP-2 CT + TT blood pressure was significantly increased compared to CC genotype in all the patients. The combined presence of MMP-2 T and the MMP-7 A alleles compared to MMP-2 C and MMP-7 A alleles significantly increased the risk of preeclampsia by 3.08-fold. Our findings demonstrate an association between the MMP-2 C-735 T polymorphism with blood pressure and the risk of preeclampsia. Also, in the presence of polymorphism total antioxidant capacity level decreased in severe preeclampsia.Impact statementWhat is already known on this subject: Matrix metalloproteinases (MMPs) including MMP-2 might be involved in the pathogenesis of preeclampsia through alteration of invasive ability of trophoblastic cells and abnormal placentation. In one available study the absence of association between MMP-2 C-735T polymorphism with gestational hypertension or preeclampsia has been reported.What the results of this study add: We found that the presence of MMP-2 C-735T polymorphism increased the risk of preeclampsia and there was a significantly lower level of total antioxidant capacity in the presence of the polymorphism in severe preeclampsia. Also, we found significantly higher systolic and diastolic blood pressures in the presence of MMP-2 C-735T polymorphism. We detected a synergism between the MMP-2 T and the MMP-7 A alleles that increased the risk of preeclampsia.What the implications are of these findings for clinical practice and/or further research: New findings of our study are involvement of lower activity MMP-2 -735 T allele and its synergism with MMP-7 A allele, low promoter activity allele, in the pathogenesis of preeclampsia through possible impairment of placentation and also by decreased total antioxidant capacity and increased blood pressure. Further association studies of the role of MMP-2 polymorphism and MMP-2 activity in relation to oxidative stress parameters and blood pressure could elucidate the role of MMP-2 and MMP-7 in the pathogenesis of preeclampsia.
Matrix metalloproteinase 9
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目的 探讨憩室病与结肠组织中基质胶原代谢的关系.方法通过生物化学方法测定14例憩室组患者和14例对照组患者结肠组织中基质胶原的总量并分别测定基质胶原Ⅰ、Ⅲ、基质金属蛋白酶(MMP)-1和MMP-13的含量.结果两组基质胶原总量差异无显著性意义(t=0.731,P》0.05).憩室组结肠组织基质胶原Ⅰ含量低于对照组,分别为(1.36±0.31)p·μm2和(1.61±0.34)p·μm2,两组比较,t=2.216,P《0.05.而憩室组结肠组织基质胶原Ⅲ含量高于对照组,分别为(1.62±0.33)p·μm2和(1.41±0.39)p·μm2,两组比较,t=2.075,P《0.05.基质胶原Ⅰ/Ⅲ的比值憩室组低于对照组,分别为0.83±0.25和1.14±0.28,两组比较,t=2.793,P《0.01.MMP-1憩室组和对照组分别为(4.81±0.91)p·μm2和(6.11±0.94)p·μm2,两组比较差异有显著性意义(t=2.458,P《0.05).两组间MMP-13的量差异无显著性意义(t=0.687,P》0.05);但MMP-13并非在所有的病例中都表达,憩室组的表达率为57.14%(8/14),对照组表达率为21.43%(3/14),两组表达率比较,X2=4.87,P《0.01.结论憩室病患者结肠组织中基质胶原Ⅰ/Ⅲ比值的降低是导致憩室病的一个重要因素,可能与MMP-1和MMP-13的异常表达有关。
Diverticulosis
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Myocardial fibrosis
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Objective To investigate the expressions of endothelin 1(ET 1), matrix metalloproteinase 3(MMP 3) and tissue inhibitor of metalloproteinase 1(TIMP 1) in human glomeruli and the related significance. Methods A total of 32 patients with primary mesangioproliferative glomerulonephritis(MsPGN) and 5 controls were included in this study. The expression levels of ET 1, MMP 3, TIMP 1 and LN proteins were determined by immunohistochemistry. Results The expressions of ET 1, MMP 3,TIMP 1 and LN proteins enhanced in normal glomeruli of moderate and severe MsPGN. The ratio of MMP 3/TIMP 1 decreased in severe MsPGN( P 0.05 or P 0.01). The expression of ET 1 was negatively correlated with the ratio of MMP 3/TIMP 1( r =-0.703, P 0.01) but positively with the expression of LN( r =0.880, P 0.01). The ratio of MMP 3/TIMP 1 was negatively correlated with the expression of LN( r =-0.623, P 0.01). Conclusion ET 1 may be involved in the decrease of the ratio of MMP 3/TIMP 1, which may contribute to the inhibition of ECM degradation in human glomeruli.
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目的 比较急性脑梗死、短暂脑缺血发作(TIA)和陈旧脑梗死患者血清基质金属蛋白酶-9(MMP-9)水平并分析其影响因素.方法 缺血性脑血管病患者136例,分为急性脑梗死组57例,TIA组22例,陈旧脑梗死组57例,进行神经功能评分及血压、血常规、血脂、血糖检查.依据ELISA法进行血MMP-9测定.结果 MMP-9水平分别为急性脑梗死患者(444.13±418.46)ng/ml,TIA患者(374.36±278.31)ng/ml,陈旧脑梗死患者(231.11±367.43)ng/ml.急性脑梗死和TIA患者血MMP-9水平明显高于陈旧脑梗死患者(P＜0.05).MMP-9水平与血白细胞水平(r=0.192,P=0.025)、低密度脂蛋白(r=0.261,P=0.002)、收缩压(r=0.232,P=0.006)呈正相关;与高密度脂蛋白(r=-0.219,P=0.011)和血糖(r=-0.254,P=0.003)呈负相关.MMP-9与收缩压(β=0.259,P=0.001)、血白细胞(β=0.209,P=0.008)、低密度脂蛋白(β=0.586,P=0.000)、胆固醇(β=-0.458,P=0.007)和血糖(β=-0.200,P=0.014)具有线性关系.结论 MMP-9水平在急性脑梗死及TIA时升高,收缩压、血白细胞和低密度脂蛋白均可能为其影响因素。
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Objective To observe the expressions of nuclear factor-kappa B (NF-κB),matrix metalloproteinase-9 (MMP-9),and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the renal tissue of rats with type 2 diabetes and investigate the effect of AT1 receptor antagonist irbesatan on the expressions of NF-κB,MMP-9,and TIMP-1 along with renal structure and function. Methods The murine model of type 2 diabetes was established by the use of STZ at a small dose. 24 rats were randomized to control group (group A),diabetes group (group B) or irbesatan group (group C),8 for each group. Immunohistochemistry and RT-PCR were used to detect the expressions of MMP-9,TIMP-1,and NF-κBp65 mRNA. Changes in renal structure and function were observed. Results The expressions of NF-κB and TIMP-1 were obviously upregulated but MMP-9 expression was downregulated in group B as compared with group A or C. The glomerular basement membrane was evidently thickened and extramesangial matrix and UAE were markedly increased in group B in comparison with group A or C while the pathological changes were less in group C than in group B. Conclusions NF-κB,MMP-9,and TIMP-1 are involved in the pathogenesis and development of diabetic nephropathy. Irbesatan plays a role in reducing proteinuria and delaying the occurrence of pathological changes in the kidney through inhibiting NF-κB activity,upregulating MMP-9 expression,and downregulating TIMP-1 expression.
Pathogenesis
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Objectives: To evaluate the association of the matrix metalloproteinase 9 (MMP) (−1562) C / T polymorphism and complex MMP 9/tissue matrix metalloproteinase 1 inhibitor (MMP9 / TIMP1) in patients with arterial hypertension (AH) Methods: 58 patients (27 men, 31 women) and 59 controls were included. There are 35 patients with AH+ Metabolic syndrome (MS) and 23 without one. Genotyping analysis of the SNP was performed using Wizardâ Genomic DNA Purification Kit Cat # A1125 (Promega, USA), followed by cyclic sequencing of the PCR fragments. Complex MMP-9 / TIMP-1 was determining by enzyme immunoassay (ELISA) using R & D Diagnostics Inc. reagents. (USA) in pg/ml Results: Genotypes CT and CT of MMP9 (−1562) occur equally frequently in groups of patients with AH and in healthy individuals (OR = 1.4, p = 0.39). The T allele of MMP9 (−1562) was significantly higher in the subgroup of patients without MS signs (OR = 2.66, p = 0.04) compared with the control group. There is no significant difference between men and women in the incidence of MMP9 (−1562). The MMP9/TIMP1 complex was 5.8 (3.7, 11.2) pg / ml in control, it was 15.0 (4.9, 219.3) pg / ml (p < 0.05) in persons with AH. The MMP9 / TIMP1 complex was 5.7 (3.7, 153.8) in men with AH, 35.0 (7.2, 268.3) in women (p < 0.05) compared with the control group and men. The MMP9 (−1562) CC genotype conforms 31.09 (7.0, 133.4) pg/ml of MMP9/TIMP1 complex, which was statistically significantly lower in comparison with the patients with the MMP9 genotype (−1562) CT + TT - 60.8 (8.0, 3382) pg/ml (p < 0.05) Conclusion: The functional polymorphism MMP-9-1562 C / T is more often in patients with AH without MS, T allele is associated with a high serum content of the complex MMP9 / TIMP1 in women as a marker of connective tissue dysmetabolism
TIMP1
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