Plasma Concentrations Of Tissue Inhibitor Research Articles

Increased serum level of high sensitivity troponin T even prior to surgery can predict adverse events during carotid endarterectomy.

Perioperative stress affects the outcome of carotid endarterectomy performed under regional anesthesia. Here we aimed to explore the temporal profile of the stress marker cortisol and its relationship to high-sensitivity troponin-T, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and S100B as an indicator of blood-brain barrier alteration in the systemic circulation. Prospective part of the study: a total of 31 patients with significant carotid stenosis scheduled for carotid endarterectomy in regional anesthesia were enrolled. Follow-up part of the study and retrospective analysis of the outcome: each patient was followed up to five years and morbidity as well as mortality data were collected from an electronic database. Blood samples from each patient were serially taken; prior to surgery (T1), at the time of reperfusion (T2), 24 h (T3) and 72 h later postoperatively (T4), then the plasma concentration of each biomarker was measured. Besides, the clinical and surgical factors and perioperative adverse events were recorded. More positive correlations were found between: the early change of S100B (T2-T1) and late change in plasma cortisol level (T4-T3) (r = 0.403; p < 0.05); the early change of cortisol (T2-T1) and the early postoperative change of plasma matrix metalloproteinase-9 level (T3-T2) (r = 0.432; p = 0.01); the plasma concentration of tissue inhibitor of metalloproteinase-1 at 24 postoperative hours and the late change in plasma high-sensitivity troponin-T level (T4-T3) (r = 0.705; p < 0.001). Five patients needed an intraoperative shunt in whom the high-sensitivity troponin-T was elevated even prior to surgery, but definitive stroke never occurred. Plasma matrix metalloproteinase-9 concentration at reperfusion independently predicted the five-year mortality with a cut-off value of 456 ng/ml (sensitivity: 86%, specificity: 84%, area 0.887, p = 0.002). A higher intraoperative change in S100B level reflecting carotid endarterectomy induced acute silent brain ischemia was associated with more pronounced post-operative change of cortisol. An early elevation of cortisol was found to be associated with a delayed increase of matrix metalloproteinase-9. Importantly, an increased high-sensitivity troponin-T even prior to carotid endarterectomy may predict clamp intolerance, and elevated matrix metalloproteinase-9 at reperfusion suggests a poor outcome.

The role of epicardial fat tissue in atrial fibrillation onset in patients with hypertension

Abstract Aim To study the influence of epicardial fat tissue (EFT) on atrial fibrillation (AF) occurrence in hypertensive patients. Materials and methods The study included 195 patients with hypertension aged from 38 to 72 years (mean age was 61.5±1.8 years). All patients were divided into two groups: group I included 95 hypertensive patients with paroxysmal AF; 100 patients with hypertension in sinus rhythm were enrolled into group II. Echocardiography was performed to evaluate the thickness of EFT in a parasternal long-axis view. The EFT volume was assessed with computed tomography (CT) scan. The plasma concentration of tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase-9 (MMP-9) was measured to evaluate the myocardial fibrosis process. Results There was no significant difference between the studied groups of patients in body mass index: 34.43±1.2 kg/m2 in group I vs 31.97±1.67 kg/m2 in the group II. Waist circumference was significantly higher in group I in comparison with the group II patients: 118.9±3.3 cm vs 110.2±1.4 cm, respectively (p=0.038). EFT thickness was significantly higher in patients with paroxysmal AF (11.6±0.8 mm) in comparison with the patients in sinus rhythm (8.6±0.4 mm) (p&amp;lt;0.001). In group I patients a significant increase of EFT volume (4.6±0.4) in comparison with II group (3.5±0.25) (p=0.002) was noted. A significant positive correlation was revealed in hypertensive patients with paroxysmal AF between EFT volume and left atrial (LA) volume (r=0.7, p=0.022). Also, the plasma concentrations of TIMP-1 and MMP-1 were significantly higher in patients with paroxysmal AF and hypertension. There was a strong positive correlation between EFT volume and plasma concentration of TIMP-1 (r=0.72; p=0.01) and between the EFT volume and the LA volume (r=0.7, p=0.022) in group I patients. Multivariate regression analysis revealed the significant influence of increased EFT thickness more than 10 mm (prevalence ratio (PR) 4.1; 95% CI 1.1; 15.6) and EFT volume more than 6 ml (PR 3.7; 95% CI 1.0; 14.2) on AF occurrence. Conclusion Increased EFT thickness (more than 10 mm) and EFT volume (more than 6 ml) are predictors of AF onset in hypertensive patients. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The complex subject of the Department

The effect of antihypertensive treatment on arterial stiffness and serum concentration of selected matrix metalloproteinases.

IntroductionThe aim of the study was to assess the arterial stiffness and serum levels of selected metalloproteinases (MMPs) in hypertensive patients and their changes following antihypertensive therapy.Material and methodsThe study group consisted of 95 patients with essential arterial hypertension (HT) stage 1 or 2 (mean age: 53.1 ±13.0 years). The control group consisted of 31 normotensives of the same age range. Hypertension patients were randomized to one of the following monotherapies for 6 months: quinapril, losartan, amlodipine, hydrochlorothiazide or bisoprolol. Carotid-femoral pulse wave velocity (PWV) was measured using a Complior device. Serum concentrations of MMPs (proMMP-1, MMP-2, MMP-3, MMP-9) and plasma concentration of tissue inhibitor of MMPs (TIMP-1) were measured using ELISA.ResultsPulse wave velocity and serum concentrations of MMP-2 and MMP-9 were higher in HT patients than in the control group. In HT patients PWV was significantly associated (R2 = 0.41) with age (B = 0.408, p = 0.00027), systolic blood pressure (SBP) (B = 0.441, p = 0.0011), and MMP-3 (B = 0.204, p = 0.0459). After 6 months of treatment, regardless of the agent used, we observed a significant decrease of PWV, SBP, MMP-2 and MMP-3 and an increase of TIMP-1 plasma concentration. The decrease of PWV was significantly associated with a decrease of SBP (R2 = 0.07, B = 0.260, p = 0.015) only.ConclusionsIn patients with arterial hypertension, beside age and systolic blood pressure, the determinants of arterial stiffness include serum MMP-3 concentration. For drugs compared in the study with the same hypotensive effect obtained, the arterial stiffness reduction effect is not dependent on the drug used. Systolic blood pressure is one of the independent factors responsible for the reduction of arterial stiffness in the course of antihypertensive treatment.

Lercanidipine Reduces Matrix Metalloproteinase-9 Activity in Patients With Hypertension

Increased levels of metalloproteinase (MMP)-9 have been shown in hypertensive patients. Lercanidipine is a calcium channel blocker with antioxidant actions. We examined whether lercanidipine produces antioxidant effects and reduces MMP-9 activity in hypertensive patients in a placebo-controlled, crossover, single-blinded design study including 18 healthy volunteers (control group), and 14 hypertensive patients without (N = 7) or with (N = 7) diabetes mellitus. Hypertensive patients were randomized to treatment with placebo (15 days) or lercanidipine 20 mg/d (15 days). Arterial blood pressure was evaluated with ambulatory blood pressure monitoring. Plasma thiobarbituric acid reactive species (TBA-RS) levels were measured to assess oxidative stress, and plasma MMP-2 and MMP-9 were assayed by gel zymography before and after treatment with placebo or lercanidipine. Plasma concentrations of tissue inhibitor of metalloproteinases (TIMP)-1 were measured by ELISA. Lercanidipine reduced mean arterial pressure by 7% in hypertensive patients without diabetes (P < 0.05), but not in hypertensive patients with diabetes. It significantly decreased plasma TBA-RS levels in hypertensive patients without and with diabetes (95% confidence interval [CI], -26 to -46%, P = 0.048, and -22 to -33%, P = 0.036, respectively). In addition, lercanidipine decreased activated MMP-9 in hypertensive patients without and with diabetes (95% CI, -19 to -47%, P = 0.047, and -80 to -96%, P = 0.010, respectively). No effects were seen on MMP-2. No significant differences or changes in plasma TIMP-1 concentrations were found. Therefore, we demonstrate for the first time that lercanidipine consistently decreased MMP-9 activity and reduced oxidative stress in hypertensive patients, thus suggesting a mechanism probably involved in the pleotropic actions of lercanidipine.

Plasma concentration of tissue inhibitor of matrix metalloproteinase 1 in patients with colorectal carcinoma.

The expression of tissue inhibitor of matrix metalloproteinase (TIMP) 1 in tumour tissue from patients with colorectal carcinoma has been reported to be related to disease progression. However, the clinical significance of plasma TIMP-1 has not been fully elucidated. The plasma level of TIMP-1 protein was determined by enzyme-linked immunosorbent assay in samples from 54 patients who underwent resection of the primary tumour. Plasma TIMP-1 levels were associated significantly with depth of invasion and metastasis to lymph nodes and liver. Circulating TIMP-1 levels were significantly higher in patients with serosal invasion, liver metastases and Dukes' stage C tumours. Using a cut-off value of 160 ng/ml, serosal invasion and Dukes' C stage could be predicted with an accuracy of 68.5 per cent. With a cut-off value of 170 ng/ml, metastasis to the lymph node and liver could be predicted with an accuracy of 66.7 and 70.4 per cent respectively. These values were greater than those for carcinoembryonic antigen and CA19-9. These data suggest that the plasma concentration of TIMP-1 correlates with both invasion and metastasis in patients with colorectal carcinoma.

Intratumoral concentrations of tissue inhibitor of matrix metalloproteinase 1 in patients with gastric carcinoma

Previously, the authors clarified that the plasma concentration of tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) in patients with gastric carcinoma was a significant predictor of tumor invasiveness and metastasis. To further clarify the clinical significance of TIMP-1, the authors used an enzyme-linked immunoassay to assess TIMP-1 protein concentrations in samples of tumor tissue from 86 patients who underwent primary resection for gastric carcinoma. Concentrations in samples of normal gastric mucosa from 73 of these patients also were assessed. Tissue TIMP-1 concentrations were significantly greater in gastric tumors than in normal gastric mucosa and were associated significantly with a variety of pathologic factors, including macroscopic type, depth of tumor invasion in the gastric wall, presence of lymphatic vessel invasion, pattern of tumor infiltration into the surrounding tissue, and disease stage. Significantly greater TIMP-1 concentrations were found in tumors that were exposed to the serosal surface compared with tumors that were limited to the submucosal layer. TIMP-1 protein was significantly greater in tumors with lymphatic vessel invasion, an infiltrative pattern into the surrounding tissue (INF-gamma), and in tumors from patients with Stage III disease. Survival was significantly poorer in patients with TIMP-1 concentrations > or = 10.0 ng/mg total protein. When patients were stratified by disease stage, survival was significantly different in patients with Stage III disease. Multivariate analysis demonstrated that intratumoral concentrations of TIMP-1 were the most significant independent factor for survival. These findings suggest that the intratumoral concentration of TIMP-1 protein may be a good indicator of tumor aggressiveness and can serve as a significant independent predictor of survival in patients with gastric carcinoma.