Metalloproteinase-1 In Patients Research Articles

Plasma levels of matrix metalloproteinases in patients with breast cancer as a potential marker of cardiotoxicity associated with doxorubicin therapy

Plasma levels of matrix metalloproteinases in patients with breast cancer as a potential marker of cardiotoxicity associated with doxorubicin therapy

Optimization of the selection of the volume of surgical intervention in cases of pronounced morphological and structural changes of the parenchyma in patients with a high risk of developing pancreatic cancer

Chronic pancreatitis is a common recurrent pathology of the pancreas. The long course of the inflammatory process, accompanied by chronicity, is often attributed to the causes that lead to the development of pancreatic cancer. The aim of the work is to study the morphological changes of the pancreas in rats and the level of matrix metalloproteinases and tissue inhibitor of metalloproteinases in patients with complicated forms of chronic pancreatitis and a high risk of developing pancreatic cancer in order to optimize the selection of the volume of surgical intervention. A histological study of the pancreas of rats with chronic pancreatitis and chronic pancreatitis on the background of diabetes was carried out. 27 patients operated on during 2020-2022 were examined. In 15 of them, we were unable to clearly and convincingly differentiate of chronic pancreatitis from pancreatic cancer, since quite often the clinical symptoms and diagnostic picture of these diseases are similar. In the remaining 12 patients it was confirmed with all the inherent clinical signs of chronic pancreatitis and ductal hypertension. Matrix metalloproteinases (MMP-1, -2, -3, -8, -9, -10) and tissue inhibitor of metalloproteinases were studied. The obtained results were processed statistically. Morphological changes of the pancreas in rats correspond to high and moderate ductal dysplasia of the PanIN 2 and PanIN 3 class, which are direct predictors of pancreatic adenocarcinoma. In 22 patients moderate and severe exocrine insufficiency was observed, confirmed by a significant decrease in fecal elastase. An intraoperative biopsy of the changed tissue of the pancreas was performed. Among the 15 operated patients of the main group, 9 were diagnosed with diabetes mellitus and changes in MMTs and a peptide pool inherent in malignant tissue. Intraoperatively, after performing a punch biopsy, acinar metaplasia was detected in 3 patients, tissue changes characteristic of PanIN2-PanIN3 in 4 patients, and pancreatic cancer in the head area was confirmed in 3 patients. Changes in the protein profile of the plasma, clinical manifestations, as well as characteristic changes in the pancreas tissue, gave us grounds for performing extended resection interventions. Studying the morphological structure of the pancreas, using as many methods as possible for differential diagnosis between chronic pancreatitis and pancreatic cancer, as well as a comprehensive approach to the patient will allow for the most correct and effective intervention.

Lung and blood perioperative metalloproteinases in patients undergoing oncologic lung surgery: Prognostic implications.

Metalloproteinases (MMPs) have been reported to be related to oncologic outcomes. The main goal of the study was to study the relationship between these proteins and the long-term prognosis of patients undergoing oncologic lung resection surgery. This was a substudy of the phase IV randomized control trial (NCT02168751). We analyzed MMP-2, -3, -7, and -9 in blood samples and bronchoalveolar lavage (LBA) and the relationship between MMPs and long postoperative outcomes (survival and disease-free time of oncologic recurrence). Survival was longer in patients who had lower MMP-2 levels than those with higher MMP-2 in blood samples taken 6 h after surgery (6.8 vs. 5.22 years; p = 0.012) and MMP-3 (6.82 vs. 5.35 years; p = 0.03). In contrast, survival was longer when MMP-3 levels were higher in LBA from oncologic lung patients than those with lower MMP-3 (7.96 vs. 6.02 years; p = 0.005). Recurrence-free time was longer in patients who had lower MMP-3 levels in blood samples versus higher (5.97 vs. 4.23 years; p = 0.034) as well as lower MMP-7 (5.96 vs. 4.5 years; p = 0.041) or lower MMP-9 in LBA samples (6.21 vs. 4.18 years; p = 0.012). MMPs were monitored during the perioperative period of oncologic lung resection surgery. These biomarkers were associated with mortality and recurrence-free time. The role of the different MMPs analyzed during the study do not have the same prognostic implications after this kind of surgery.

The content of matrix metalloproteinase-1, -9 and tissue inhibitor of matrix metalloproteinase-1 in patients with bronchial asthma and obesity

Airway remodeling is a significant factor in the progression of respiratory failure in bronchial asthma (BA). Obesity can contribute to inflammation, and consequently – airway remodeling, by increased production of matrix proteinase (MMP). However, the mechanisms of remodeling in different phenotypes of BA, especially in comorbid patients, remain poorly understood. The aim of the research was to examine the levels of remodeling markers MMP-1, MMP-9 and tissue inhibitor of matrix proteinases (TIMP-1) in obese asthmatic patients, taking into account their age at the onset of BA, the severity of symptoms and the level of control. Material and methods. 195 patients with BA associated with obesity were examined. The control group consisted of 95 practically healthy people. Patients were divided into two groups: Group I included 100 patients with early onset, and Group II included 95 patients with late onset of BA. The study was approved by the Bioethics Commission of the Medical Institute of Sumy State University. Statistical analysis of the obtained results was carried out using the SPSS-17 program. Results. The content of MMP-1, -9 and TIMP-1 was higher in patients with early (129.40 ± 7.86; 177.30 ± 9.19; 142.40 ± 12.22 ng/ml, respectively) and late (196.60 ± 9.62; 289.80 ± 16.23; 187.50 ± 11.34 ng/ml, respectively) BA with obesity compared to practically healthy individuals (р < 0.005). Patients with late-onset BA associated with obesity likely had higher indicators than those with early BA. In patients with early BA, the levels of MMP-1, -9, and TIMP-1 were not significantly different depending on the severity of the disease (р > 0.05). However, in patients with severe late BA, the levels of these markers were higher compared to those with mild BA (р < 0.05). Levels of MMP-1 and MMP-9 in patients with early-onset and late-onset BA with obesity were higher in the absence of disease control compared to those in complete and partial control, but in late-onset exceeded those in early-onset. Conclusions. Considering the obtained results, it can be assumed that the level of MMP-1, MMP-9 and TIMP-1 in obese patients with BA can serve as biomarkers of airway remodeling, namely, the severity and the level of BA control.

PORTO-001 study: Changes in the oral microbiome and matrix metalloproteinases in patients with oropharyngeal squamous cell carcinoma undergoing definitive chemoradiotherapy.

e18034 Background: Head and neck cancer patients treated with concurrent chemoradiotherapy (CRT) develop oral mucositis, with varying severity. However, knowledge about risk factors, biomarkers, treatment, and prognosis of oral mucositis is still limited. Methods: We designed an exploratory study to examine the changes in the oral microbiome and salivary and plasma levels of matrix metalloproteinases (MMP) in patients with locoregionally advanced oropharyngeal squamous cell carcinoma (OPSCC) undergoing definitive CRT. Patients were followed from screening to week 7 of treatment with CRT, which consisted of 70 Gy/35 fractions of radiation with cisplatin given at 100 mg/m2 q3weeks or weekly 40 mg/m2. Clinical and demographic data were collected at specified timepoints. Samples were collected at screening and on week 4 of treatment with CRT. A tumor swab was collected for microbiome analysis. Blood and saliva samples were collected for measurements of 7 MMPs and 26 other cytokines. The study population was summarized descriptively. The change in the cytokines and the α-diversity of microbiome data (week 4 vs screening) were examined using Wilcoxon signed rank test. Results: A total of 11 patients were included. Nine (82%) were male. 5 patients (45%) were stage III, and there were 2 patients (18%) for each of stages I, II, and IV. A history of smoking was present in 5 (45.4%) patients. p16 was positive in 9 (81.8%) patients. There was a median weight loss of 7.0% (5.1 kg) between screening and week 7 visits. Almost half (45%) of patients developed grade 2 oral mucositis. All patients developed radiation dermatitis, with most cases ranging between grades 2 and 3. There were no statistically significant changes in the salivary levels of cytokines. However, 1 patient developed clinical oral mucositis before all the other patients, at week 1, and this was associated with an upsurge in the salivary levels of IFN-γ, IL-6, TNF-α, MMP-1, MMP-2 and MMP-7. For all patients, there were statistically significant changes (median (95% confidence interval)) in the blood plasma levels of IP-10 (-0.1 fluorescence intensity (FI) (-0.3, -0.04), p = 0.01), MIP-1ß (0.2 FI (0.07, 0.5), p = 0.02), SDF-1α (1.4 pg/ml (0.07, 3.7), p = 0.02), MMP-1 (-0.4 pg/ml (-0.5, -0.09), p = 0.01), MMP-3 (0.4 pg/ml (0.03, 0.5), p = 0.02), and MMP-8 (-0.2 FI (-0.3, -0.02), p = 0.04). There was a 29.1% ((-3.0%, -32.8%), p = 0.005) reduction in α-diversity of microbiome at week 4 from screening. Conclusions: In this small series of patients diagnosed with OPSCC, there was a change in the plasma levels of IP-10, MIP-1ß, SDF-1α, MMP-1, MMP-3, and MMP-8, as well as a reduction in the α-diversity of the oral microbiome. Larger studies are needed to confirm these results. If confirmed, these changes might imply a potential role as predictive or pharmacodynamic biomarkers for oral mucositis.

Serum Levels of Matrix Metalloproteinases in Patients Undergoing Endovascular Intervention for Peripheral Arterial Disease

Matrix metalloproteinases (MMPs) play a significant role in the development and progression of atherosclerotic vascular disease. The purpose of this study was to measure and document the profile of plasma-circulating MMPs in patients with peripheral arterial disease (PAD) undergoing endovascular revascularization. This was a single-center prospective observational study with 80 patients with PAD enrolled. They underwent percutaneous balloon angioplasty and/or angioplasty with stent. Exclusion criteria were acute limb ischemia, active inflammation, wet gangrene, liver disease, end-stage renal failure, and cancer. Patients that underwent open or hybrid (open and endovascular) approach were also excluded from the study. Venous blood samples were taken preoperatively, 24hr, and 6months postoperatively. The values of MMP-2, MMP-3, MMP-7, MMP-9, and their inhibitors (tissue inhibitor of metalloproteinases [TIMP]), TIMP-1 and TIMP-2 were measured. The mean age was 67.1years, and 66 of them (82.5%) were male. During the clinical follow-up (mean 35.8% months), 12 patients died (16.4%), 15 (20.5%) of them had a major adverse limb event (MALE), and 14 (19.2%) of them had a major adverse cardiovascular event (MACE). There was a statistically significant rise in the values of MMP-2, MMP-3, and MMP-7 at 6months postoperatively, when compared to the preoperative and 24hr postoperative values. There was no correlation of MMP and TIMP values with mortality, MALE, and MACE events. The present single-center prospective study documented increased circulating levels of MMPs postoperatively in PAD patients undergoing endovascular treatment. Vascular trauma caused by angioplasty could trigger the expression of MMPs and TIMPs, but the absence of any association with clinical complications requires further investigation.

The association of vitamin D status with oxidative stress biomarkers and matrix metalloproteinases in patients with knee osteoarthritis.

The association of vitamin D status with osteoarthritis (OA) has been demonstrated previously. The current study was performed to examine the association of vitamin D status with oxidative stress markers and matrix metalloproteinases (MMPs) in patients with knee OA. This case-control study was conducted on 124 subjects with mild to moderate knee OA and 65 healthy controls. Demographic data was collected from all participants at baseline. Serum levels of vitamin D as well as markers of oxidative stress including malondialdehyde (MDA), total oxidant status (TOS), superoxide dismutase (SOD), oxidative stress index (OSI), paraoxonase-1 (PON-1), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC) were evaluated for each participant. Furthermore, serum concentrations of MMP-1, MMP-3, MMP-13, and cartilage oligomeric matrix protein (COMP) were measured. The results of the present study indicated that individuals with vitamin D insufficiency had higher levels of MDA, TOS, SOD, and OSI as well as lower levels of PON-1 and TAC. Based on the linear regression analysis, serum vitamin D levels were inversely correlated with MDA, TOS, SOD, OSI, MMP-1, and MMP-13 and positively associated with TAC levels (p < 0.0001). Patients with sufficient vitamin D levels had lower MMP-1 and MMP-13 levels compared to patients with vitamin D insufficiency (p < 0.001 and p < 0.001, respectively). Findings from this study showed a strong association between vitamin D deficiency and increased oxidative stress and MMPs activity in patients with knee OA.

Expression of matrix metalloproteinase in patients with Alzheimer and mechanism of huangqi granule (astragalus saponins) intervention

This study investigated expression of matrix metalloproteinases in senile dementia patients and mechanism of Huangqi granule intervention. 78 cases of senile dementia patients were selected as observation group from June 2017 to June 2019, while 62 cases of healthy people were enrolled as control group. Blood samples were collected after admission and levels of matrix metalloproteinase 3,9,13 (MMP-3,9,13) were determined. The observation group was randomly and equally assigned into donepezil hydrochloride group and combined drug group. Mental state examination (MMSE) and Boston diagnostic aphasia test (BDAE) were used to compare the two groups. Montreal Cognitive Assessment (MoCA), Dementia Scale (HDS) scores, biochemical index levels and drug safety were also used. MMP-2, MMP-9 and urinary plasminogen activator levels in observation group were higher and ZO-1 was lower than control group along with higher MMP-3,9,13 mRNA levels (p &lt; 0.05) which were reduced after 3 months of treatment. MMSE scale, BDAE, MoCA, and HDS scores in the combined drug group were higher after 3 months of treatment (p &lt; 0.05). The level of NSE (neuron-specific enolase) was higher and SOD level was lower than in the donepezil hydrochloride group (p &lt; 0.05); nausea and vomiting, muscle spasms, insomnia bradycardia and gastrointestinal bleeding incidence in two groups showed no differences (p &gt; 0.05). The intervention of Huangqi granules can improve cognitive function of patients, inhibit matrix metalloproteinase, thereby improving the level of biochemical indicators without increasing the incidence of complications.

Prognostic value of matrix metalloproteinases in patients with anthracycline-induced heart failure

Highlights. Elevated levels of matrix metalloproteinases 2 and 9 are associated with the initiation and severity of CHF developed after breast cancer therapy with anthracyclines, which may contribute to cardiac remodeling and the progression of systolic dysfunction. Concentrations of matrix metalloproteinases-2 and -9 in blood serum serve as predictors of the unfavorable course of anthracycline-induced heart failure.Aim. To assess the role of matrix metalloproteinases-2 (MMP-2) and 9 (MMP-9) in the development and course of anthracycline-induced chronic heart failure (CHF) during 24 months of observation.Methods. The study included 114 women 12 months after completion of chemotherapy (CT) for breast cancer and developed CHF. The control group (n = 70) consisted of women (mean age 45.0 [42.0; 50.0] years old) who received doxorubicin as part of chemotherapy, but they did not develop CHF 12 months after completion of chemotherapy. The levels of biomarkers (MMP-2, MMP-9, NT-proBNP) in blood serum were determined using a sandwich immunoassay.Results. Patients with CHF had signs of cardiac remodeling and higher values of NT-proBNP, MMP-2 and MMP-9 (p&lt;0.001) than women from the control group. After 24 months of observation, all patients with CHF were divided into 2 groups: group 1 – women with an unfavorable course of CHF (n = 54), group 2 – women with favorable course of pathology (n = 60). Criteria for the unfavorable course of CHF: the emergence of new or worsening of existing symptoms/signs of heart failure; and/or hospitalization due to HF decompensation; decrease in left ventricular ejection fraction by more than 10%; or an increase in the functional class of CHF by 1 or more. Baseline echocardiographic parameters and NT-proBNP values did not differ in groups 1 and 2. Levels of MMP-2 were higher by 8% (p = 0.017) and MMP-9 by 18.4% (p&lt;0.001) in group 1. In 1 group the level of MMP-2 decreased after 24 months of observation. In group 2 the level of MMP-2 increased by the end of the observation period. MMP-2 levels ≥388.2 pg/ml (sensitivity 46%, specificity 80%; AUC = 0.64; p = 0.013) and MMP-9 ≥21.3 pg/ml (sensitivity 86%, specificity 84.4%; AUC = 0.9; p&lt;0.001) were determined as predictors of an unfavorable course of CHF.Conclusion. Remodeling of the extracellular matrix may play an important role in the pathogenesis of CHF initiated by drugs of the anthracycline class. Elevated levels of MMP-2 and MMP-9 in the blood serum are associated with an unfavorable course of anthracycline-induced CHF and can be recommended when assessing the risk of an unfavorable course of pathology.

FEATURES OF EXPRESSION OF GROWTH MEDIATORS AND MATRIX METALLOPROTEINASES AT THE LOCAL LEVEL IN PATIENTS WITH LOWER LIMB VARICOSE VEINS, CLINICAL CLASS C4 - C6

The purpose of the research was to study the features of the expression of growth mediators and matrix metalloproteinases in patients with lower limb varicose veins, clinical classes C4-C6. The study included 98 patients. The control group consisted of 102 healthy donors. The levels of VEGF, PDGF, matrix metalloproteinases (MMP-2, MMP-9), superoxide dismutase, and prolidase were studied. The average value of VEGF in pathologically altered vein (PAV) wall samples was 40.1 ± 6.2 ng/g of protein and was statistically significantly higher - 1.7 times compared with the same value in persons from CG 2 (23.0 ± 5.9 ng/g protein, p=0.001). Patients with lower limb varicose veins (LLVV) showed an inverse correlation between VEGF levels and SOD activity in blood plasma and PAV (r=-0.52; p=0.002 and r=-0.59; p=0.001, respectively). An increase in the level of PDGF correlated with an increase in the oxidative stress index (OSI) in the blood plasma and the PAV wall (r=0.59; p=0.022 and r=0.61; p&lt;0.001). In patients with LLVV, a high level of MMP-9 inversely correlated with the total oxidant capacity (TAC) in blood plasma and in the varicose vein wall (r=-0.48; p&lt;0.001 and r=-0.52; p=0.012). In patients with LLVV, there were statistically significant relationships between prolidase activity and OSI and TAC values ​​in the PAV wall (r=0.62; p=0.003 and r=-0.59; p&lt;0.001). It has been established that VEGF, PDGF, MMPs play a key role in the LLVV pathogenesis; the dynamics of these indicators can be used to predict the effectiveness of surgical treatment and the risk of recurrence.

Doxycycline can reduce glycocalyx shedding by inhibiting matrix metalloproteinases in patients undergoing cardiopulmonary bypass: A randomized controlled trial.

Cardiopulmonary bypass (CPB) leads to shedding of the glycocalyx of endothelial cells, resulting in a series of complications such as tissue edema and coagulatory and microcirculatory dysfunctions. Matrix metalloproteinases (MMPs) can cause glycocalyx shedding in a variety of pathological processes, but their role in the process of CPB is still unclear. We hypothesized that the MMPs inhibitor doxycycline would reduce glycocalyx shedding by inhibiting MMPs during CPB. Thirty-six patients were randomized to receive either 100mg oral doxycycline (an MMPs inhibitor) or a matching placebo pill twice a day for three days before CPB. The primary outcome was the concentration of plasma syndecan-1. Secondary outcomes included heparan sulphate, MMP-2, MMP-9, ratio of urinary albumin to creatinine, and short-term clinical outcomes. In order to further prove that MMPs in plasma caused the glycocalyx shedding, human umbilical vein endothelial cells were cultured with plasma obtained from cardiac surgery patients before or after CPB (with or without MMPs inhibitor GM6001). The change in glycocalyx content was detected by immunofluorescence. CPB resulted in an increase of MMPs and shedding of the glycocalyx. Plasma syndecan-1 was higher in the control group than in the doxycycline group (median difference:15.04μg/L; 95% CI: 9.14-20.94μg/L; P<0.001). Similar to syndecan-1, plasma heparan sulphate, MMP-2, and MMP-9 concentrations in the doxycycline group were significantly lower than those in the control group during CPB. Doxycycline was also correlated with a reduction in the ratio of urinary albumin to creatinine and improved the short-term clinical outcomes of patients. Endothelial cells cultured with plasma from patients after CPB showed significant shedding of syndecan-1 and heparan sulphate (post-CPB group vs pre-CPB group, P<0.001). GM6001 was shown to reduce shedding of syndecan-1 and heparan sulphate by inhibiting MMPs (post-CPB+GM6001 group vs post-CPB group, P<0.001). Doxycycline can reduce glycocalyx shedding by inhibiting MMPs during CPB.

Serum concentration of matrix metalloproteinase-1 in patients with preterm labor compared to gestational age matched controls

Serum concentration of matrix metalloproteinase-1 in patients with preterm labor compared to gestational age matched controls

Comparative description of the levels of matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1 in patients with 5D stage chronic kidney disease and in patients with anterior abdominal wall hernias

Objective. To determine the levels of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the plasma of patients with 5D stage chronic kidney disease (CKD) and in patients with anterior abdominal wall hernias.Materials and methods. Patients with end-stage chronic kidney disease and patients with anterior abdominal wall hernias were included into the study. MMP-1 and TIMP-1 plasma concentrations were determined by enzyme-linked immunosorbent assay.Results. The analysis of the plasma of the patients with end-stage CKD and with anterior abdominal wall hernias shows a statistically significant increase in the level of MMP-1 when compared to that of the patients of the comparison group: 7.98 ng / ml and 8.35 ng / ml, respectively (p ˂ 0. 0001). The plasma level of TIMP-1 (158.85 ng / ml) was statistically significantly higher in the patients with 5D CKD than in the patients with anterior abdominal wall hernias — 33.16 ng / ml and in the comparison group — 73.46 ng / ml (p ˂ 0.001). At the same time, the TIMP-1 level was determined statistically significantly higher in the comparison group than in the patients with anterior abdominal wall hernias (p ˂ 0.001).Conclusion. The obtained patterns may indicate an increased breakdown of type I collagen and interstitial substance in patients in the end-stage of CKD and in patients with anterior abdominal wall hernias.

The role of matrix metalloproteinases in patients with pulmonary hypertension: data from a prospective study

BackgroundDespite several therapies, pulmonary hypertension (PH) is still a severe disease which can lead to right heart failure. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in cardiac and vascular remodeling in PH. Therefore, these biomarkers play an important role in PH patients. This study investigated whether TIMP-4, MMP-2, and N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) plasma levels are useful in assessing the severity of PH and other clinical or echocardiographic parameters.MethodsThe concentrations of MMP-2, TIMP-4, and NT-proBNP in 68 PH patients were compared with those of 12 controls without PH. All patients underwent a physical examination, echocardiography, and were checked for the presence of cardiovascular risk factors; also, plasma concentrations of MMP-2, TIMP-4, NT-proBNP, total cholesterol, and triglycerides were determined.ResultsIn PH patients, significantly elevated plasma levels of TIMP-4 (PH: 2877.99 ± 1363.78 pg/ml, control: 2028.38 ± 762.67 pg/ml, p = 0.0068) and NT-proBNP ( PH: 2405.00 pg/ml—5423.47 ± 6703.38 pg/ml, control: 411.0000 pg/ml—421.75 ± 315.37 pg/ml, p = 0.01) were detected. We also observed that MMP-2 and NT-proBNP were significantly increased in patients with higher WHO functional class (p = 0.001 for MMP-2, p = 0.008 for NT-proBNP), higher pressure in the pulmonary artery (p = 0.002 for MMP-2, p = 0.001 for NT-proBNP), and more severe tricuspid regurgitation (p = 0.001 for MMP-2, p = 0.009 for NT-proBNP). TIMP-4 was elevated in patients with more severe pressure in the pulmonary artery (p = 0.006).ConclusionsThe plasma levels of TIMP-4 and NT-proBNP are higher in PH patients. MMP-2 and NT-proBNP correlates with different PH parameters severity (WHO functional class, sPAP severity, TV regurgitation severity). Therefore, plasmatic levels of MMP-2 and NT-proBNP at this kind of patients reflect disease severity and may have a prognostic role. MMP-2 can help assess the beneficial effects of PH pharmacotherapy on tissue remodeling. These remodeling biomarkers may not have a diagnostic value but they have the potential to predict survival. Nevertheless, a greater understanding of the involvement of MMPs in PH is mandatory to further explore the prognostic role and the possibilities of therapeutic MMP inhibition in PH.

The effect of surgery on the levels of matrix metalloproteinases in patients with inguinal hernia.

Matrix metalloproteinases (MMPs) are associated with the alteration of extracellular matrix. The purpose of this study was to investigate how the levels of matrix metalloproteinases and their inhibitors - TIMPs are influenced by the presence of inguinal hernia as well as by its surgical treatment. The studied group consisted of 25 patients with inguinal hernia and 21 healthy controls for comparison. Two blood samples - before and after the treatment were collected from patients. Serum concentrations of MMPs and TIMPs were analysed by multiplex immunoassays. There was a difference in circulating levels of MMPs in patients before the surgery compared to healthy controls - the concentrations of MMP-2 and MMP-9 were significantly lower (p=0.026, p=0.018, respectively). After the surgery, the levels of MMPs, especially MMP-2 (p<0.0001), were significantly decreased in patients compared to the preoperative values, apart from MMP-9. On the contrary, MMP-9 showed significant increase after the surgery (p<0.0001). Circulation levels of TIMP-2 in patients were significantly decreased in comparison with controls (p=0.004), whereas levels of TIMP-1 were similar to controls. Both tested metalloproteinase inhibitors showed a significant decrease in detected levels (TIMP-1 p=0.0004; TIMP-2 p<0.0001) after the procedure compared to the preoperative values. The levels of MMPs, especially MMP-2 and MMP-9, and their inhibitors TIMP-1 and TIMP-2 are involved by the presence of inguinal hernia as well as are influenced by the surgery.

Elastography and Metalloproteinases in Patients at High Risk of Preterm Labor.

Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Its etiopathology is multifactorial; therefore, many of the tests contain the assessment of the biochemical factors and ultrasound evaluation of the cervix in patients at risk of preterm delivery. The study aimed at evaluating the socioeconomic data, ultrasound examinations with elastography, plasma concentrations of MMP-8 and MMP-9 metalloproteinases, and vaginal secretions in the control group as well as patients with threatened preterm delivery (high-risk patients). The study included 88 patients hospitalized in the Department of Obstetrics and Pregnancy Pathology, SPSK 1, in Lublin. Patients were qualified to the study group (50) with a transvaginal ultrasonography of cervical length (CL) ≤ 25 mm. The control group (38) were patients with a physiological course of pregnancy with CL > 25 mm. In the study group, the median length of the cervix was 17.49 mm. Elastographic parameters: strain and ratio were 0.20 and 0.83. In the control group, the median length of the cervix was 34.73 mm, while the strain and ratio were 0.20 and 1.23. In the study group, the concentration of MMP-8 in the serum and secretions of the cervix was on average 74.17 and 155.46 ng/mL, but in the control group, it was significantly lower, on average 58.49 and 94.19 ng/mL. The concentration of MMP-9 in both groups was on the same level. Evaluation of the cervical length and measurement of MMP-8 concentration are the methods of predicting preterm delivery in high-risk patients. The use of static elastography did not meet the criteria of a PTB marker.

Plasma levels of tissue inhibitor of metalloproteinase-1 in patients with type 1 diabetes mellitus associate with early diabetic neuropathy and nephropathy.

Background:Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been suggested as a marker for abnormal regulation of tissue remodelling in type 1 diabetes. Metalloproteinase-9 (MMP-9) has been associated with matrix turnover, and Neutrophil gelatinase associated lipocalin (NGAL) is a marker of tubular injury in diabetic nephropathy. The aim was to analyse these biomarkers to unmask early diabetic complications.Methods:Thirty-three type 1 diabetes patients, aged 20–35 years, and disease duration 20 ± 5.3 years were included. Along with clinical examination, neurophysiological measurements, routine biochemistry, plasma concentrations of TIMP-1, MMP-9 and NGAL were determined with immunoenzymatic techniques.Results:TIMP-1 correlated with abnormal unilateral and bilateral vibratory sense foot perception (r = −0.49 and r = −0.51, respectively), foot neuropathy impairment assessment score (NIA; r = −0.55), neuropathy symptom assessment score (r = 0.42), microalbuminuria (r = 0.50) and eGFR (r = −0.45). MMP-9 correlated with impaired foot NIA (r = 0.51). Multiple regression analysis showed an association for TIMP-1 (p = 0.004) with impaired neurophysiological examinations and renal dysfunction along with NGAL (p = 0.016 and p = 0.015 respectively).Conclusions:This study suggests that plasma levels of TIMP-1, MMP-9 and NGAL may serve as useful biomarkers in unravelling subclinical neuropathy and nephropathy in type 1 diabetes.

Concentrations of metalloproteinase-1 in patients with morphea treated with phototherapy: a preliminary study.

Morphea (localized scleroderma) is a rare, chronic, inflammatory connective tissue disease, characterized by immune system dysfunction, vasculopathy and skin fibrosis. One of the most effective treatments is phototherapy. Phototherapy has been found to be effective in treating localized scleroderma by inducing the expression of metalloproteinase-1. To compare the concentrations of metalloproteinase (MMP-1) before psoralen and ultraviolet A (PUVA) and ultraviolet A1 (UVA1) treatments in the serum of patients with morphea. The observational study was conducted in one research centre and included patients with generalised morphea who were treated with PUVA and UVA1 phototherapies. The mean age of all morphea patients included in the study was 55.7 years. The levels of MMP-1 were examined by ELISA (The Biorbyt Human MMP-1 ELISA - Enzyme-Linked Immunosorbent Assay). The study showed that patients treated with PUVA and UVA1 had an improvement based on clinical measures, resulting in a reduction of clinical score. However, we did not observe statistically significant differences in MMP-1 concentrations before and after treatment. Limitations: The study sample was relatively small. Further studies on a larger group of patients would be beneficial. Our data suggest that there is a possible correlation between MMP-1 concentrations and phototherapy. MMP-1 levels were found to be increased following phototherapy treatment, which may suggest a correlation with better response to treatment in patients with morphea. However, further research is needed.

Gene variability in matrix metalloproteinases in patients with recurrent aphthous stomatitis.

The development of recurrent aphthous stomatitis (RAS), inflammatory disease of oral mucosa, is influenced by both environmental and genetic factors. The aim of this study was to investigate polymorphisms located in seven genes coding different types of matrix metalloproteinases (MMPs)-collagenases (MMP1, MMP8, and MMP13), gelatinases (MMP2 and MMP9), stromelysin (MMP3), and membrane-type metalloproteinase (MMP16) in patients with RAS and healthy controls. Totally, 223 subjects were included in this case-control study and their detailed anamnestic, clinical, and laboratory parameters were recorded. Seventy-seven patients with RAS and 146 controls were genotyped for seventeen polymorphisms in the MMPs genes using the real-time polymerase chain reaction (PCR) or PCR with restriction analysis. Allele, genotype, and haplotype frequencies of the studied polymorphisms between RAS patients and controls were similar, except for allele distributions of MMP1 rs1144393, MMP9 rs3918242, and MMP16 rs10429371, which were different between patients with RAS and healthy controls (P=.023, P=.049 and P=.025, all Pcorr >0.05, respectively). Moreover, the comparison of genotype frequencies (TT vs CC+CT) of the MMP16 rs10429371 variant showed a marginally significant difference between RAS patients and controls (P=.05, Pcorr >0.05, OR=1.68, 95% CI=0.95-2.98). No significant relationship between investigated polymorphisms in seven MMPs genes and RAS development in the Czech population was observed in this study.

Matrix metalloproteinases in patients with resistant hypertension and type 2 diabetes mellitus: relation with renal blood flow and kidney function

Objective.To evaluate the plasma levels of metalloproteinases (MMP) and their inhibitor in patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (DM2) and their relationship with renal blood flow and kidney function.Design and methods.The study included 18 patients with RHTN and DM2 and 16 individuals with RHTN without DM, who underwent offce and 24-h ambulatory blood pressure measurements, renal Doppler ultrasound, and laboratory tests (daily albuminuria, estimated glomerular fltration rate calculated by CKD-EPI formula, HbА1c and basal glycaemia levels, MMP-9, MMP-2, tissue inhibitor of MMP type 1 (TIMP1), MMP/TIMP-1 ratios).Results.Patients with RHTN and DM2 and subjects with RHTN without DM were comparable by mean levels of metalloproteinases, TIMP-1, and their ratios. The frequency of increased MMP-9 level was similar in both groups (61 % for RHTN + DM2 group and 75 % for RHTN without DM, p &gt; 0,05). In patients with RHTN and DM2 the increase in MMP-9 and a decrease in TIMP-1/MMP-9 ratio were associated with a reduction in renal resistive indices (MMP-9 and RI in the main renal arteries: right-sided R = –0,60, p = 0,009, left-sided R = –0,60, p = 0,008; in segmental arteries: R = –0,49, p = 0,038 on the right and R = –0,59, p = 0,012 on the left; for TIMP-1/MMP-9 and segmental arteries: R = 0,51, p = 0,028 on the right; and R = 0,46, p = 0,04 on the left). The eGFR and MMP-9 signifcantly correlated (R = 0,55, p = 0,023). Patients with increased albuminuria showed higher values of TIMP-1/MMP-2 ratio than patients with normal albuminuria (2,97 ± 0,82 и 1,58 ± 0,33 ng/mL, respectively, p = 0,03). There was a direct correlation between TIMP-1/MMP-2 ratio and basal glycaemia (R = 0,59, p = 0,018).Conclusions.Patients with RHTN and DM2 had comparable MMP levels and their inhibitor to those in patients with RHTN without DM, which may partly reflect that extracellular matrix formation is independent from carbohydrate disorders in RHTN. In patients with RHTN and DM2 an increase in MMP-9 and a decrease in TIMP-1/MMP-9 ratio may be adaptive, since it is accompanied by improved intrarenal blood flow and renal fltration function. The increase in basal hyperglycemia is associated with the suppression of the proteolytic activity of MMP-2 related to the progression of albuminuria.