Serum Levels Of Matrix Metalloproteinase-9 Research Articles

Minocycline and matrix metalloproteinase inhibition in acute intracerebral hemorrhage: a pilot study.

Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disorder with high morbidity and mortality. Minocycline is a matrix metalloproteinase-9 (MMP-9) inhibitor that may attenuate secondary mechanisms of injury in ICH. The feasibility and safety of minocycline in ICH patients were evaluated in a pilot, double-blinded, placebo-controlled randomized clinical trial. Patients with acute onset (<12 h from symptom onset) ICH and small initial hematoma volume (<30 ml) were randomized to high-dose (10 mg/kg) intravenous minocycline or placebo. The outcome events included adverse events, change in serial National Institutes of Health Stroke Scale score assessments, hematoma volume and MMP-9 measurements, 3-month functional outcome (modified Rankin score) and mortality. A total of 20 patients were randomized to minocycline (n = 10) or placebo (n = 10). The two groups did not differ in terms of baseline characteristics. No serious adverse events or complications were noted with minocycline infusion. The two groups did not differ in any of the clinical and radiological outcomes. Day 5 serum MMP-9 levels tended to be lower in the minocycline group (372 ± 216 ng/ml vs. 472 ± 235 ng/ml; P = 0.052). Multiple linear regression analysis showed that minocycline was associated with a 217.65 (95% confidence interval -425.21 to -10.10, P = 0.041) decrease in MMP-9 levels between days 1 and 5. High-dose intravenous minocycline can be safely administered to patients with ICH. Larger randomized clinical trials evaluating the efficacy of minocycline and MMP-9 inhibition in ICH patients are required.

Possible Association between Serum Matrix Metalloproteinase-9 (MMP-9) Levels and Relapse in Depressed Patients following Electroconvulsive Therapy (ECT).

BackgroundMatrix metalloproteinases are involved in neuroinflammatory processes, which could underlie depression. Serum levels of MMP-9 and MMP-2 in depressed patients are significantly altered following electroconvulsive therapy, but an association between altered matrix metalloproteinases after successful ECT and possible relapse has yet to be investigated.MethodsSerum was obtained twice, before and immediately after a course of electroconvulsive therapy, from 38 depressed patients. Serum was also collected, once, from two groups of age- and gender-matched healthy controls, 40 volunteers in each group. Possible associations between levels of matrix metalloproteinases and relapse during a 1-year follow-up period were analyzed.ResultsExcluding patients who did not respond to electroconvulsive therapy and patients lost to follow-up, data from 28 patients were evaluated. Eighteen of the patients (64.3%) relapsed within 1 year. In the group that did not relapse, serum levels of MMP-9 were significantly decreased after a course of electroconvulsive therapy, but not in the group that relapsed. No association between MMP-2 and relapse was observed.ConclusionThe degree of change in serum MMP-9 change could be associated with relapse following electroconvulsive therapy in depressed patients.

Dampness-Heat Accelerates DMBA-Induced Mammary Tumors in Rats.

To investigate the impact of dampness-heat (DH) on the development of mammary tumors in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats. Forty rats were randomly divided into 3 groups in a randomized block design, including the control group (n=13), DMBA group (n=14), and DMBA plus DH group (n=13). Rats in the DMBA group and DMBA plus DH group were intragastrically administrated with DMBA (100 mg/kg) for twice, once per week, while rats in the control group were treated with equivalent volumes of sesame oil. After DMBA administration, rats in the DMBA plus DH group were exposed to a simulated climate chamber with ambient temperature (33.0±0.5°C) and humidity (90%±5%) for 8 weeks, 8 h per day. The body weight, time of tumor formation, and number of tumors were measured weekly to calculate tumor incidence, average latency period, average number of tumors, and average tumor weight. At the end of the experiment, the levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in serum, and the contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β in serum and tumor tissue were measured, respectively. Some tumor tissues were processed for hematoxylin-eosin staining to determine the histopathological changes. Compared with DMBA, DMBA plus DH significantly increased the average number of tumors, average tumor weight, levels of serum MMP-9, TIMP-1, TNF-α and IL-1β, and contents of tumor tissue TNF-α and IL-1β (P<0.05 or P<0.01). DH could accelerate the development of mammary tumors through increasing the expressions of MMP-9, TIMP-1, TNF-α and IL-1β in DMBA-induced rats.

ВПЛИВ ПРОГРЕСУВАННЯ ФІБРИЛЯЦІЇ ПЕРЕДСЕРДЬ НА РІВЕНЬ МАТРИКСНОЇ МЕТАЛОПРОТЕЇНАЗИ-9

Фібриляція передсердь (ФП) одне з найбільш частих захворювань у клінічній практиці. Результати експериментальних та клінічних досліджень показали наявність взаємозв’язку між ФП і змінами передсердних електричних властивостей.Мета дослідження – вивчити рівень матриксної металопротеїнази-9 (ММП-9) та оцінити її значення і роль на різних етапах розвитку ідіопатичної фібриляції передсердь (ФП).Матеріали і методи. У дослідженні взяли участь пацієнти з ідіопатичною формою ФП. Відповідно до ступеня прогресування захворювання, їх поділили на 3 групи: пароксизмальну, персистуючу та хронічну ФП. Контрольну групу склали практично здорові пацієнти. Для визначення сироваткового рівня ММП-9 використовували імуноферментний аналіз подвійними антитілами з ферментною міткою.Результати досліджень та їх обговорення. Кожна досліджувана група включала 20 пацієнтів, контрольна група склала 40 хворих. Рівень ММП-9 у досліджуваних групах значно відрізнявся від контрольної і склав: (170,62±24,65), (202,33±29,18), (252,3±21,87) нг/мл для пароксизмальної, персистуючої та хронічної форм ФП і (75,78±14,7) нг/мл – у контрольній групі відповідно. У міру прогресування захворювання рівень ММП-9 підвищувався (р&lt;0,05).Висновки. Підвищення рівня ММП-9 вірогідно асоціюється з розвитком і прогресуванням ідіопатичної ФП.

The efficacy of microsurgery in the treatment of cerebral aneurysm rupture and its effect on NF-κB, MCP-1 and MMP-9.

The clinical efficacy of microsurgical neck clipping for the treatment of cerebral aneurysm rupture and its effect on serum nuclear factor κ-light-chain-enhancer of activated β cells (NF-κB), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) levels were investigated. A total of 56 patients with first occurrence of cerebral aneurysm rupture were enrolled from June 2015 to June 2016. These patients were divided into control (25 patients) and observation groups (31 patients) according to treatment received. The patients in the control group were treated with interventional embolization and extraventricular drainage, while the patients in the observation group were treated with microsurgical neck clipping. Serum NF-κB, MCP-1 and MMP-9 levels were measured by ELISA prior to the operation and at 6 h post-operation. Clinical effects were compared at the 6-month follow-up. There was no significant difference in the success rate of the operation between the two groups (p>0.05). The incidence of complications in the observation group was significantly lower than that in the control group (p<0.05). The Glasgow Outcome Scale score was significantly improved in the observation group (p<0.05) compared with the control group. Serum NF-κB, MMP-9 and MCP-1 were significantly decreased in both groups at 6 and 24 h after operation, but the observational group showed significantly lower levels for all three proteins than the control group (p<0.05). The application of early microsurgical neck clipping for the treatment of cerebral aneurysm rupture can reduce complications and improve clinical prognosis, and this may be related to a decrease in serum inflammatory response-related factors (NF-κB and MCP-1) and MMP-9.

Steroid therapy and renal dysfunction are independently associated with serum levels of matrix metalloproteinase-3 in patients with rheumatoid arthritis

Objective: This study aimed to evaluate whether the level of serum matrix metalloproteinase-3 (MMP-3), a marker of synovium inflammation, is affected by clinical characteristics of patients in rheumatoid arthritis (RA) patients.Methods: We analyzed data from 1087 female patients with RA. Pearson’s correlation coefficients were calculated to explore associations between variables. Stepwise multiple linear regression analysis was performed to evaluate patient background variables that could potentially affect serum MMP-3 levels.Results: Serum MMP-3 was moderately correlated with C-reactive protein (CRP) (r: 0.478). Factors that independently influenced serum MMP-3 levels were CRP (β: 0.450), prednisolone (PSL) use (β: 0.100), estimated glomerular filtration rate (eGFR) (β: −0.085), swollen joint count assessed on 28 joints (β: 0.072), and body mass index (β: −0.061) in female patients with RA. In RA patients with PSL use, factors that independently influenced serum MMP-3 levels were CRP (β: 0.480), eGFR (β: −0.175), and PSL dose (β: 0.171).Conclusions: Our findings suggest that steroid therapy and renal dysfunction affect serum MMP-3 levels in patients with RA.

Sex-related differences in serum matrix metalloproteinase-9 screening non-calcified and mixed coronary atherosclerotic plaques in outpatients with chest pain.

The objective of this study is to evaluate the clinical feasibility of serum matrix metalloproteinase-9 (MMP-9) for screening plaque composition as assessed by coronary computed tomography angiography (CCTA) in outpatients with chest pain,and the effects of sex on this feasibility. Eight hundred and sixty-two consecutive outpatients with chest pain were divided into three groups according to the results of CCTA: non-plaque (NP, n=474), calcified plaques (CPs, n=179), non-calcified and mixed plaques (NCPs and MPs, n=209). We found that serum MMP-9 levels were significantly higher in patients with NCPs and MPs compared to those with either NP or CPs, especially in women (649.7±279.8 vs. 485.7±231.6ng/mL or 515.7±274.5ng/mL, P<0.001). MMP-9 showed better identification of NCPs and MPs than other related factors and was an independent predictor for NCPs and MPs both in women and men. The receiver operating characteristic analysis indicated a substantial superiority in women with area under the curve of 0.75 (95% CI 0.69-0.82, P<0.01), compared with men of 0.59 (95% CI 0.53-0.65, z=3.71, P<0.01). The diagnostic tests revealed a moderate risk of the presence of NCPs and MPs with MMP-9 ≥531.6ng/mL in female patients.

Is cardiovascular disease in patients with diabetes associated with serum levels of MMP-2, LOX, and the elastin degradation products ELM and ELM-2?

Background: Diabetes mellitus type 2 (T2DM) is a significant risk factor for the development of cardiovascular diseases (CVDs). In a previous microarray study of internal mammary arteries from patients with and without T2DM, we observed several elastin-related genes with altered mRNA-expression in diabetic patients, namely matrix metalloproteinase 2 (MMP-2), lysyl oxidase (LOX) and elastin itself. In this study we investigate whether the serum concentrations of elastin-related proteins correlate to signs of CVD in patients with T2DM.Methods: Blood samples from 302 type 2 diabetic patients were analysed for MMP-2, LOX, and the elastin degradation products ELM and ELM2. The results were investigated for correlations to signs of CVD in different vascular territories, as determined by myocardial perfusion scintigraphy, carotid artery thickness and ankle-brachial blood pressure index.Results: T2DM patients with peripheral arterial disease (low ankle-brachial index) (PAD) display higher levels of MMP-2 and ELM compared to patients without PAD. However, none of the proteins or degradation products correlated with myocardial ischemia or a combined measure of CVD-signs, including myocardial ischemia, increased carotid thickness and decreased ankle-brachial blood pressure.Conclusions: Our results suggest that the diabetic environment affects the circulating amounts of MMP-2 and ELM in patients with PAD. However, the same connection could not be seen in diabetic patients with CVD broadly identified in three vascular territories. LOX and ELM-2 did not correlate to any type of CVD. Overall, serum levels of elastin-related molecules are only remotely related to CVD in type 2 diabetes.

Obstructive sleep apnoea and related comorbidities in incident idiopathic pulmonary fibrosis.

The objectives of this prospective study were: 1) to determine the prevalence and determinants of obstructive sleep apnoea (OSA) in patients with newly diagnosed idiopathic pulmonary fibrosis (IPF); 2) to determine whether OSA was associated with cardiovascular disease (CVD) as well as increased oxidative stress and levels of IPF biomarkers in the blood.A group of 45 patients with newly diagnosed IPF attended polysomnography. The prevalence of CVD and the severity of coronary artery calcification were investigated by high-resolution computed tomography. The levels of 8-hydroxydeoxyguanosine (8-OH-DG) and various IPF biomarkers in the blood were compared between patients with no or mild OSA (apnoea-hypopnoea index (AHI) <15 events·h-1), with moderate OSA (15 ≤AHI <30 events·h-1) and with severe OSA (AHI ≥30 events·h-1).The prevalence of moderate-to-severe OSA and severe OSA was 62% and 40%, respectively. AHI did not correlate with demographic or physiological data. All patients with severe OSA had a medical history of CVD, versus 41.2% and 40% of those with no or mild OSA, or with moderate OSA, respectively (p<0.0001). Ischaemic heart disease (IHD) and moderate-to-severe coronary artery calcifications were strongly associated with severe OSA. The 8-OH-DG and matrix metalloproteinase-7 serum levels were significantly increased in the severe OSA group.Moderate-to-severe OSA is highly prevalent in incident IPF and severe OSA is strongly associated with the presence of CVD, particularly IHD.

Quantitative evaluation of atherosclerotic plaques and intraplaque neovascularization using contrast-enhanced ultrasound after treatment with atorvastatin in rabbits

IntroductionThis study is supposed to investigate the value of contrast-enhanced ultrasound (CEUS) in quantitative evaluation of atherosclerotic plaques and intraplaque neovascularization after treatment with atorvastatin (ATV) in rabbits. Material and methodsForty-five New Zealand white rabbits were enrolled to construct the rabbit model of AS. All rabbits were assigned into the control, AS group and ATV groups (n=15 individually). The AS plaque formation and relative parameters were observed and calculated by CEUS respectively. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured. Serum levels of matrix metalloproteinase-3 and 9 (MMP-3/9) and high-sensitivity C-reactive protein (hs-CRP) were examined by ELISA. The histological changes plaques, maximal plaque thickness (MPT), plaque area (PA) and corrected plaque area (PA/CVA) were evaluated by HE staining. Immunohistochemistry (IHC) was used to measure the positive protein expressions of VEGF, FVIII-Rag, MMP-3, CD40L and F8. The correlation between CEUS parameters with ELISA and IHC was analyzed by the Spearman correlation analysis. ResultsAt the 8th week, no plaque and new blood vessel were observed in the control group. The ATV group showed more plaques and new blood vessels, and lower IMT, plaque thickness and area than the AS group. The PI and RI were significantly increased in the AS and ATV groups compared to the control group. PI, RI. Plaque EI and its ratio in plaque and arterial lumen of the ATV group were lower than those in the AS group. Compared with the control group, the AS and ATV groups had higher serum levels of TC, TG, LDL, MMP-3, MMP-9 and hs-CRP, and higher AI. However, compared with AS group, serum levels of TC, TG, LDL and AI fell in ATV group. In comparison of the AS group, serum levels of MMP-3, MMP-9 and hs-CRP, MPT, PA and PA/CVA, and the positive expressions of VEGF, FVIII-Rag, MMP-3, CD40L and F8 were significantly reduced in the ATV group. The AS and ATV groups showed a positive correlation of EI in the plaque and its ratio in the plaque and arterial lumen with F8 protein expression, MMP-3 and MMP-9. ConclusionIn conclusion, our results indicated that ATV stabilizes atherosclerotic plaques and reduces intraplaque neovascularization in a rabbit model with AS, which can be characterized using CEUS.

Circulating tumor cells and serum levels of MMP-2, MMP-9 and VEGF as markers of the metastatic process in patients with high risk of metastatic progression.

Metastases are a severe complication in cancer patients and biomarkers predicting their progression are still lacking for specific groups of patients. HER2 positive breast cancer (HER2 BC) patients on trastuzumab therapy are at risk of the development of unpredictable and often fatal central nervous system (CNS) metastases and castration resistant prostate cancer (CRPC) patients urgently need a marker of disease progression during therapy. Proposed metastatic markers: circulating tumor cells (CTC), serum levels of matrix metalloproteinase 2 (MMP-2), 9 (MMP-9) and vascular endothelial growth factor (VEGF) were prospectively studied to confirm their utility in these two narrowly defined groups of cancer patients. The groups comprised 44 advanced HER2 BC, 24 CRPC patients and 42 healthy controls. An immunomagnetic separation method followed by PCR and electrophoretic detection (AdnaGen, Germany) were used for CTC determination. Serum marker levels were determined by the ELISAs (R&D System, USA). MMP-2 serum level was significantly higher in HER2 BC patients who developed CNS metastases, especially if there were also bone metastases. CTCs were a negative predictive marker for overall survival in HER2 BC patients. MMP-9 serum level was significantly higher in CRPC patients in whom disease progression occurred. CTC vanished from the blood of most of the CRPC patients (from 88% to 37%) during chemotherapy. MMP-2 serum level and CTCs show the potential to predict CNS metastases and overall survival in BC patients. CTCs and MMP-9 serum level could be a promising therapy response marker in CRPC patients.

High rate of improvement in serum matrix metalloproteinase-3 levels at 4 weeks predicts remission at 52 weeks in RA patients treated with adalimumab

Objective: This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA).Methods: Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP) < 2.3) at 52 weeks were evaluated by multivariate logistic regression analysis.Results: DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382–0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002–1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively.Conclusion: Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.

Clinical and pathogenetic features of congenital heart disease in newborns with intrauterine infection

Aim. Investigation of the features of diagnosis and treatment of congenital heart disease in newborns with intrauterine herpes and cytomegalovirus infections. &#x0D; Methods. A comparative analysis of risk factors, clinical signs and dynamics of serum levels of matrix metalloproteinases in 91 newborns with congenital heart disease during the early neonatal period was performed. All patients were divided into 2 groups: group 1 (study group) - 51 patients with congenital heart disease and intrauterine Herpes or Cytomegalovirus infection, group 2 (comparison group) - 40 children with heart disease without the signs of intrauterine infection. The control group consisted of 20 relatively healthy full-term newborns. &#x0D; Results. Mothers of children with congenital heart disease and intrauterine infection more often compared to mothers of children from group 2 had inflammatory disease of reproductive system (49.1 and 22.5% respectively, р ≤0.05), medical abortions in past medical history (84.3 and 27.5% respectively, р ≤0.01), acute respiratory viral infections during pregnancy (21.6 and 7.5% respectively, р ≤0.05). Levels of matrix metalloproteinase 9 in umbilical blood plasm were statistically significantly increased in all newborns with congenital heart disease compared to control levels. The highest concentration of enzyme was registered in patients with congenital heart disease and nervous system disorders associated with intrauterine infection and in newborns with severe heart disease. Inflammatory extracardial changes in patients with congenital heart disease associated with intrauterine infection caused by Herpes Simplex virus and Cytomegalovirus were accompanied by significant increase of matrix metalloproteinase 8. &#x0D; Conclusion. The association between matrix metalloproteinase 9 in blood serum of newborns and clinical signs of a congenital heart disease during early neonatal period was revealed; high levels of metalloproteinase 8 can indicate intrauterine infection in newborns with congenital heart disease during early neonatal period.

Spondyloarthritis: Matrix Metalloproteinasesas Biomarkers of Pathogenesis and Response to Tumor Necrosis Factor (TNF) Inhibitors.

The term spondyloarthritis (SpA) is used to describe a group of multifactorial chronic inflammatory diseases characterized by a predisposing genetic background and clinical manifestations typically involving the sacroiliac joint. The absence of pathognomonic clinical and/or laboratory findings generally results in a delay in diagnosis and, consequently, in treatment. In addition, 20–40% of SpA patients are non-responders to tumor necrosis factor (TNF) inhibitor therapies. Given these considerations, it is important to identify biomarkers that can facilitate the diagnosis and assessment of disease activity. As inflammation plays a key role in the pathogenesis of SpA, inflammatory mediators have been investigated as potential biomarkers for diagnosing the disease and predicting response to therapy. Some investigators have focused their attention on the role of matrix metalloproteinases (MMPs), which are known to be markers of synovial inflammation that is generated in the joint in reaction to inflammatory stimuli. Several studies have been carried out to verify if serum MMPs levels could be useful to diagnose SpA, to assess disease severity, and to predict response to TNF inhibitor therapy. The current review focuses on MMPs’ role in SpA pathogenesis, diagnosis and therapeutic implications.

Serum levels of matrix metalloproteinase-3 and autoantibodies related to rheumatoid arthritis in the general Japanese population and their association with osteoporosis and osteoarthritis: the ROAD study.

To purpose of this study was to reveal the mean levels and positive proportion of serological markers related to rheumatoid arthritis, and clarify their relationship with osteoporosis and hand osteoarthritis (OA). A total of 1546 participants from the third survey of the research on osteoarthritis/osteoporosis against disability study were enrolled in the current study. Using participant blood samples, the levels of anti-cyclic citrullinated protein (CCP) antibody, rheumatoid factor (RF), matrix metalloproteinase-3 (MMP-3), C-reactive protein (CRP), and high-sensitivity CRP (hsCRP) were measured. Subjects with higher than normal levels were defined as being positive. Osteoporosis was defined according to the recommendations set by World Health Organization criteria in 1994. Radiographic hand OA was evaluated using the modified Kellgren-Lawrence (KL) scale. The positive proportion of anti-CCP antibody, RF, MMP-3, CRP, and hsCRP was 1.8, 7.1, 15.0, 6.7, and 6.4%, respectively. MMP-3 was associated with age, and was significantly higher in men than in women. Positive MMP-3 was not significantly related to osteoporosis or severe hand OA (KL grade ≥3) after adjustment for other factors including age, sex, and body mass index. The results from this study clarified the values and positive proportion of RA-related markers and revealed their relationship with osteoporosis and hand OA.

Matrix metalloproteinase 2 (MMP-2) levels are increased in active acromegaly patients.

During follow-up of acromegaly patients, there is a discordance rate of 30% between the measurements of growth hormone and insulin-like growth factor-1 levels. Further tests are required to determine disease activity in patients with discordant results. This study was planned to investigate an association of serum levels of matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B with disease activity in acromegaly patients. In this study, 64 acromegaly patients followed in our clinic were divided into two groups according to the 2010 consensus criteria for cure of acromegaly as patients with active disease (n = 24) and patients with controlled disease (n = 40). Serum matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B levels were measured by the enzyme-linked immunosorbent assay method. The mean serum matrix metalloproteinase-2 level was significantly higher in the active acromegaly patients than in the controlled acromegaly patients (150.1 ± 54.5 ng/mL vs. 100.2 ± 44.6 ng/mL; p < 0.0001). There was no significant difference between the active and controlled acromegaly patients regarding serum matrix metalloproteinase-9 and cathepsin B levels (p = 0.205 and p = 0.598, respectively). Serum matrix metalloproteinase-2 levels of 118.3 ng/mL and higher had a sensitivity of 75% and a specificity of 77.5% in determining active disease. The risk of active acromegaly was 3.3 fold higher in the patients with a matrix metalloproteinase-2 level of >118.3 ng/mL than in the patients with a matrix metalloproteinase-2 level of <118.3 ng/mL. In this study, serum matrix metalloproteinase-2 level is increased in the active acromegaly patients and a threshold value in determining active disease was defined for serum matrix metalloproteinase-2 level. This study is the first to compare acromegaly patients having active or controlled disease in terms of matrix metalloproteinase-2 and matrix metalloproteinase-9 levels. The results need to be confirmed by a study that will be conducted in a larger patient group also including a healthy control group to demonstrate the value of this novel marker in disease activity.

Mechanical Strain Induced Expression of Matrix Metalloproteinase-9 via Stretch-Activated Channels in Rat Abdominal Aortic Dissection.

BackgroundThe aim of the study was to investigate the expression of matrix metalloproteinase-9 (MMP-9) in rat abdominal aortic dissection (AD) induced by mechanical strain, so as to offer a better understanding of the possible mechanisms of AD.Material/MethodsExperimental AD in rats was achieved by the injection of porcine pancreatic elastase. At days 0, 1, 3, 5, 7, 14, 21, and 30 after the establishment of AD model, serum MMP-9 levels were measured by enzyme-linked immunosorbent assay (ELISA). Four groups of vascular rings were stretched in vitro with a mechanical strength of 0 g, 1 g, 3 g, or 5 g for 30 min. Another four groups were pretreated with GdCl3, streptomycin, SN50, and SN50M, followed by stretching with 3 g for 30 min. The messenger RNA and the protein of MMP-9 were analyzed by real-time RT-PCR and Western blotting, and NF-κB p65 was detected by ELISA.ResultsAfter the establishment of rat abdominal AD model, the serum MMP-9 levels of AD groups increased significantly. The results showed increased expression of MMP-9 in rat AD vessels stretched with mechanical strength of 1 g, 3 g, and 5 g, but this effect was mostly blocked by Gd Cl3 and streptomycin. The NF-κB activity in aortic rings was activated by stretching with a mechanical strength of 3 g and was blocked by SN50, but not by SN50M.ConclusionsThe expression of MMP-9 in serum was increased significantly after rat abdominal AD formation. Mechanical strain induced MMP-9 expression in AD vessels, which was mediated through the activation of the stretch-activated channel-induced NF-κB pathway.

Altered serum level of matrix metalloproteinase-9 and its association with decision-making in eating disorders.

The aims of this study were to determine whether the serum levels of precursor brain-derived neurotrophic factor (proBDNF), mature BDNF (mBDNF), and matrix metalloproteinase-9 (MMP-9) are altered in patients with eating disorders (ED), including anorexia nervosa (AN) and bulimia nervosa (BN), and to explore whether those levels are associated with decision-making abilities. Nineteen women with AN, 28 women with BN, and 22 age-matched healthy control women (HC) were enrolled in the current study. All participants had their decision-making abilities assessed using the Iowa Gambling Task (IGT). Their eating-related pathophysiology and depressive/anxiety symptoms were also evaluated. The MMP-9 level in AN was significantly lower than that in either BN or HC, but the serum levels of proBDNF and mBDNF did not differ among the three groups. Investigation of the serum levels of proBDNF and MMP-9 in patients with ED and controls revealed a significant correlation between them. In the BN, there were positive correlations between mBDNF level and IGT performance and also between MMP-9 level and IGT performance, but these correlations did not occur in AN. The MMP-9 level was positively associated with the Symptom Scale, one of the subscales of the Bulimic Investigatory Test, Edinburgh, only in AN. These results suggest that the serum level of MMP-9 plays a role in the pathophysiology of AN, and both the serum levels of mBDNF and MMP-9 may be associated with decision-making abilities in patients with BN.

Matrix Metalloproteinase-9 and Recovery of Acute Ischemic Stroke

Stroke outcome can be predicted by clinical features, biochemical parameters, and some risk factors. Matrix metalloproteinase-9 (MMP-9) is involved in various stages of stroke pathology. MMP-9 inhibitors are potential stroke therapeutic agents. Little is known about the relation between MMP-9-after the acute stage-and clinical recovery. The study aimed to investigate the serum level of MMP-9 at stroke onset as predictor of stroke outcome and the relation between the level of MMP-9 after 30 days and stroke recovery. The National Institutes of Health Stroke Scale, modified Rankin Scale, and serum level of MMP-9 were assessed in 30 patients with acute ischemic stroke during the first 24 hours of onset and then a month later. None of the patients received thrombolytic therapy. Thirty normal volunteers of matched age and sex were included in the control group. The serum level of MMP-9 at stroke onset was independently positively correlated with stroke outcome. The serum level of MMP-9 30 days after stroke onset was positively correlated with initial stroke severity and outcome, as well as with clinical recovery. Higher serum level of MMP-9 at stroke onset can be a predictor of poor stroke outcome. However, beyond the acute stage, MMP-9 may play beneficial role in stroke recovery.

Serum Matrix Metalloproteinase-7 Level is Associated with Fibrosis and Renal Survival in Patients with IgA Nephropathy

Background/Aims: In view of the latest findings that matrix metalloproteinase-7 (MMP-7) acted as a vital marker and pathogenic mediator of renal fibrosis in a murine model, we hypothesized that serum MMP-7 level might serve as a noninvasive prognostic biomarker in IgA nephropathy (IgAN) patients. Methods: We conducted a retrospective follow-up study of 244 IgAN patients for a median of 81.9 months. Serum MMP-7 was detected at the time of diagnosis, and renal progression was assessed by Cox proportional hazards method. Results: Compared with healthy populations, the serum levels of MMP-7 were significantly elevated in IgAN patients. Besides, serum MMP-7 levels were well correlated with renal scarring lesions characterized by glomerular sclerosis and interstitial fibrosis. Follow-up analyses revealed that increased serum MMP-7 levels were linked with a greater risk of poor renal outcome with a hazard ratio of 1.898 per doubling MMP-7 concentration. By contrast with the first quartile, the risk of deterioration in renal function elevated such that the hazard ratio for the second quartile was 1.805, 3.383 for the third, and 5.173 for the fourth quartile of the MMP-7 level. Conclusions: This study showed that the higher serum MMP-7 levels were independently associated with renal fibrosis and poor prognosis in IgAN.