基质金属蛋白酶与冠状动脉斑块稳定性相关研究

目的 :探讨基质金属蛋白酶 1(MMP 1)、基质金属蛋白酶抑制剂 1(TIMP 1)、TIMP 1/MMP 1与冠状动脉 (冠脉 )粥样硬化斑块稳定性的相关性。方法 :以冠脉血管内超声检出冠脉粥样硬化斑块的软硬特性 ,将急性冠脉综合征患者分为不稳定斑块组 (n =2 2 )和稳定斑块组 (n =12 )。测定两组间血浆MMP 1、TIMP 1浓度 ,并与冠脉血管内超声测定的斑块大小、斑块纤维帽厚度、脂核或无回声带大小、脂核或无回声带与斑块比及面积狭窄率进行相关性分析。结果 :在冠状静脉窦血和外周血中 ,不稳定斑块组MMP 1浓度明显大于稳定斑块组 (P <0 0 1) ,TIMP 1/MMP 1明显小于稳定斑块组 (P <0 0 0 1) ,有非常显著性差异。血浆MMP 1浓度与纤维帽厚度呈负相关 ,与脂核或无回声带面积、脂核与斑块比和面积狭窄率呈正相关 ,与斑块大小无关。TIMP 1/MMP 1与纤维帽厚度、面积狭窄率呈正相关 ,与脂核或无回声带面积、脂核与斑块比呈负相关。结论 :MMP 1和TIMP 1/MMP 1与冠脉斑块不稳定性呈密切相关 ,可望作为冠脉斑块不稳定性的参考指标。     

Increased ratio of serum matrix metalloproteinase-9 against TIMP-1 predicts poor wound healing in diabetic foot ulcers

ObjectiveLittle is known about serum concentrations of Matrix Metalloproteinase-9 (MMP-9), MMP-2, TIMP-1 and TIMP-2 in diabetic patients with foot ulcers. This study demonstrates their relationship with wound healing.MethodsNinety-four patients with diabetic foot ulcers were recruited in the study. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured at the first clinic visit and the end of 4-week treatment and followed up till 12 weeks. According to the decreasing rate of ulcer healing area at the fourth week, we divided those cases into good and poor healers. Through analyses, we explore the possible relationship among those factors and degree of wound healing.ResultsThe median level of serum MMP-9 in good healers was lower than poor healers at first visit (124.2 μg/L vs 374.6 μg/L, p < 0.05), and after 4-week therapy it decreased 5-fold approximately. In contrast, the change in MMP-9 concentration did not reach statistical significance in poor healers. MMP-2, TIMP-1 and TIMP-2 varied slightly in both good healers and poor healers. The MMP-9/TIMP-1 ratio better reflected the healing than MMP-9 alone before therapy and after 4 week treatment (r = ? 0.6475 vs ? 0.3251, r = ? 0.7096 vs ? 0.1231, respectively). Receiver Operator Curve (ROC) showed that the cutoff for MMP-9/TIMP-1 ratio at < 0.395 best predicted a reduction in wound area of 82% at the end of 4-week treatment with a sensitivity of 63.6% and a specificity of 58.6% (area under the curve 0.658, p < 0.001).ConclusionsDetecting serum MMP-9/TIMP-1 ratio on admission might be a predictor of healing and might provide a novel target for the future therapy in diabetic foot ulcers.     

Clinical implications of elevated serum interleukin-6, soluble CD40 ligand, metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in patients with acute ST-segment elevation myocardial infarction

BACKGROUND: Atherosclerosis is widely accepted as a chronic inflammatory disease. Research paid much attention to sensitive specific serum biomarkers for vulnerable plaques. The markers not only serve as diagnostic tools for the identification of patients with acute coronary syndrome (ACS), but also help us to identify high-risk patients. However, the existing data are limited and have been conflicting. HYPOTHESIS: Circulating interleukin-6 (IL-6), soluble CD40 ligand (sCD40L), metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) might correlate with the onset and the cardiac mortality of patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Serum levels of IL-6, sCD40L, MMP-9, and TIMP-1 were measured by sandwich enzyme-linked immunosorbent assay (ELISA) in 263 patients with STEMI and 262 age- and gender-matched control subjects without coronary artery disease (CAD). The patients with STEMI were then followed prospectively for 24 mo for the occurrence of cardiac mortality. RESULTS: Compared with the control subjects, patients with STEMI exhibited higher levels of IL-6 (p < 0.001), sCD40L (p < 0.001), MMP-9 (p < 0.001), TIMP-1 (p = 0.045), and MMP-9/TIMP-1 ratio (p = 0.007). Significant and positive correlations between MMP-9 and TIMP-1 (r = 0.610, p相似文献   

Serum levels of matrix metalloproteinase-2, -9, and vitamin D in patients with multiple sclerosis with or without herpesvirus-6 seropositivity

In recent years, extreme attention has been focused on the role of human herpesvirus-6 (HHV-6) in multiple sclerosis (MS) pathogenesis. However, the pathogenesis of MS associated with HHV-6 infection remains unknown. In this study, we measured the serum levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection. Five hundred sixty (including 300 females and 260 males) MS patients along with 560 healthy subjects were analyzed for HHV-6 seropositivity using enzyme-linked immunosorbent assay (ELISA). Subsequently, we measured the serum levels of MMP-2, MMP-9, and vitamin D levels in MS patients with HHV-6 infection and MS patients without HHV-6 infection by ELISA. About 90.7% of MS patients (508/560) were seropositive for HHV-6, while 82.3% (461/560) of healthy subjects were seropositive for this virus (p = 0.001). Moreover, there was a significant increase in the levels of MMP-2, MMP-9, and lower vitamin D in the serum samples of MS patients when compared with healthy subjects. Additionally, we demonstrated that the MMP-9 levels in seropositive MS patients were significantly higher than seronegative MS patients (p = 0.001). Finally, our results demonstrated that the mean of expanded disability status scale (EDSS) in seropositive MS patients was significantly higher in comparison to seronegative MS patients (p < 0.05). In conclusion, we suggest that the HHV-6 infection may play a role in MS pathogenesis.     

Plasma matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, and CD40 ligand levels in patients with stable coronary artery disease

Endogenous matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), are important mediators of extracellular matrix remodeling, which is integral to plaque progression in coronary artery disease. In addition, high levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. We hypothesized that circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were abnormal in patients who had stable coronary artery disease, and these levels were compared with those in matched controls. We also hypothesized correlations of MMPs, TIMPs, and sCD40L to each other and to high-sensitivity C-reactive protein (a proinflammatory marker), white blood cell count, severity of coronary artery disease (based on angiographic measurements of atherosclerotic burden), and coronary collateralization. We studied 204 adult patients who attended our unit for outpatient diagnostic cardiac catheterization for the investigation of suspected coronary artery disease. Coronary angiograms were scored for atheroma burden and stenosis by 2 independent observers. Circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were measured by enzyme-linked immunosorbent assay. Plasma levels of MMP-9 (p = 0.0099), TIMP-2 (p = 0.0019), and sCD40L (p <0.001), but not TIMP-1 (p = 0.463) were high in patients compared with healthy controls. In patients who had coronary artery disease, MMP-9 and high-sensitivity C-reactive protein levels were significantly higher in women than in men. Only MMP-9 correlated modestly with total white blood cell count (Spearman's correlation, r = 0.274, p = 0.002). Logistic regression of cardiovascular risk factors showed that only white blood cell count was independently associated with MMP-9 (p = 0.02). After standardizing for atheroma and stenosis scores, there were no statistically significant differences in our research indexes in patients who had angiographic collaterals compared with those who did not. In conclusion, stable coronary artery disease is associated with abnormal circulating levels of MMP-9, TIMP-2, and sCD40L, which do not appear to related to each other or to severity of coronary artery disease or collateralization. The gender difference in high-sensitivity C-reactive protein and MMP-9 levels may provide insight into the pathophysiology of coronary artery disease in men and women, and further studies are warranted to explore this potential link.     

Liver fibrosis improvement in chronic hepatitis C after direct acting-antivirals is accompanied by reduced profibrogenic biomarkers–a role for MMP-9/TIMP-1

Background and aimsDisturbances in matrix metalloproteinases (MMPs) and corresponding tissue inhibitors (TIMPs) contribute to hepatitis C virus (HCV)-induced fibrosis. This study aimed to determine MMP-9/TIMP-1 levels in addition to MMP-2 and -9 activities; correlating with the improvement of liver fibrosis in patients under direct-acting antiviral (DAA) therapy.MethodsClinical and laboratory follow-up were performed before treatment and after 12 weeks post-treatment, referred as sustained viral response (SVR). We evaluated liver function including non-invasive fibrosis measurements; MMP activity by zymography; and MMP-9/TIMP-1 complex, inflammatory and pro-fibrogenic mediators by immunoenzymatic assays.ResultsCohort included 33 patients (59.5 ± 9.3 years, 60.6% females) whose reached SVR and 11 control-paired subjects (42.5 ± 15 years, 54.5% females). Before treatment, HCV patients presented higher MMP-9/TIMP-1 levels (P < 0.05) when compared to controls, and the highest values were observed in patients with fibrosis (P < 0.05). In addition, MMP-9/TIMP-1 levels were significantly reduced after DAA therapy (P < 0.0001) and were associated with profibrogenic biomarkers. No differences were observed for MMP-2 and -9 activities; however, these biomarkers were significantly associated with inflammatory mediators.ConclusionOur data suggest that MMP-9/TIMP-1 complex can be a promising biomarker of active fibrogenesis, being able to identify the interruption of fibrosis progression after HCV eradication.     

急性冠脉综合征患者血浆sCD40L与血清基质金属蛋白酶水平的变化及其意义

目的：观察急性冠脉综合征（ACS）患者可溶性CD40配体（sCD40L）及血清基质金属蛋白酶-9（MMP-9）、血清组织金属蛋白酶抑制物-1（TIMP-1）水平变化及其相关性。方法：采用酶联免疫吸附法测定70例冠心病患者[ACS患者35例、稳定型心绞痛（SAP）患者35例]、35例非冠心病患者（正常对照组）sCD40L、MMP-9、TIMP-1的水平。结果：与正常对照组及SAP组比较,ACS组sCD40L[（2.73±0.92）μg/ml比（3.05±0.98）μg/ml比（4.72±1.15）μg/ml]、MMP-9[（152.38±54.22）ng/ml比（341.12±69.96）ng/ml比（574.2±139.20）ng/ml]水平明显升高（P均〈0.01）,而TIMP-1[（415.92±13.96）ng/ml比（249.32±36.80）ng/ml比（172.20±40.10）ng/ml]水平明显降低（P〈0.01）;且MMP-9与sCD40L呈正相关（r=0.42,P〈0.05）。结论：急性冠脉综合征患者可溶性CD40配体、血清基质金属蛋白酶-9水平升高,血清组织金属蛋白酶抑制物-1水平下降提示这两指标与粥样斑块不稳定相关,可作为判断粥样斑块不稳定的血清学指标。     

Serum levels of MMP-9 and TIMP-1 in primary hypertension and effect of antihypertensive treatment

BackgroundMatrix metalloproteinases, a family of proteolytic enzymes are thought to be involved in extracellular matrix accumulation during development of hypertensive target organ disease. The present study was designed to compare hypertensive patients with normotensive individuals with respect to serum levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and to search for the effect of antihypertensive treatment on the serum enzyme levels.MethodsThirty-three patients with stage 1 primary hypertension and sixteen age- and sexmatched control subjects were enrolled into the study. Serum MMP-9 and TIMP-1 levels were assessed in the hypertensive group before and after a 3-month-antihypertensive treatment (candesartan 8 mg/day to 17 patients and lisinopril 10 mg/day to 16 patients).ResultsPre-treatment serum MMP-9 levels were higher in the hypertensive group (p = 0.309) while serum TIMP-1 levels were lower (p = 0.296). Serum MMP-9 levels were decreased (p < 0.001) and TIMP-1 levels were increased (p = 0.022) after the antihypertensive treatment.ConclusionsIn hypertensive patients, increased MMP-9 activity could result in increased degradation of elastin relative to collagen and non-elasticity, while decreased TIMP-1 activity could lead to accumulation of poorly cross-linked, immature and unstable fibril degradation products, which result in misdirected deposition of collagen. Our study is important for revealing the role of the MMP enzyme system in the pathogenesis of hypertensive target organ disease.     

Matrix metalloproteinases and diabetic foot ulcers: the ratio of MMP-1 to TIMP-1 is a predictor of wound healing

Aims Matrix metalloproteinases (MMPs) play a major role in wound healing: they can degrade all components of the extracellular matrix. In diabetic foot ulcers there is an excess of MMPs and a decrease of the tissue inhibitors of MMPs (TIMPs). This imbalance is probably one cause of impaired healing. However, little is known about changes in MMPs during wound healing. Methods Sixteen patients with neuropathic diabetic foot ulcers participated. Wound fluid was collected regularly during the 12-week follow-up period, for measurement of MMP-1, MMP-2, MMP-8, MMP-9 and TIMP-1. Results were analysed by the degree of wound healing: good healers (defined by a reduction of at least 82% in initial wound surface at 4 weeks) and poor healers (reduction of less than 82% in wound surface at 4 weeks). Results In good healers, levels of MMP-8 and -9 secreted by inflammatory cells decreased earlier. The initial levels of MMP-1 were similar in good and poor healers (P = 0.1) but rose significantly at week 2 in good healers (P = 0.039). There was a significant correlation between a high ratio of MMP-1/TIMP-1 and good healing (r = 0.65, P = 0.008). Receiver Operator Curve (ROC) analysis showed that an MMP-1/TIMP-1 ratio of 0.39 best predicted wound healing (sensitivity = 71%, specificity = 87.5%). Conclusions A high level of MMP-1 seems essential to wound healing, while an excess of MMP-8 and -9 is deleterious, and could be a target for new topical treatments. The MMP-1/TIMP-1 ratio is a predictor of wound healing in diabetic foot ulcers.     

Matrix Metalloproteinases and Tissue lnhibitors of Matrix Metalloproteinases in Sputum from Patients with Bronchial Asthma

To examine a possibility that matrix metalloproteinases (MMPs) participate in the pathogenesis of asthma and/or the development of asthma attack, we measured the concentrations of MMP-2, MMP-9, and their respective tissue inhibitors of metalloproteinases (TIMP)-2 and TIMP-1, in induced sputa collected from 28 patients with moderate to severe bronchial asthma. Specimens were collected during both the attack and the remission from 15 age- and sex-matched healthy control subjects. The concentration of MMP-9 was significantly (p < 0.05) higher in the patients, even during the remission, as compared to that in healthy controls. The concentrations of MMP-9 (p < 0.05) and its specific inhibitor TIMP-1 (p < 0.01), and MMP-2 (p < 0.01) in these patients during the attack were significantly higher than those in healthy controls. In these patients, the MMP-9 concentration was significantly higher (p < 0.05) during the attack than during the remission. These results suggest that MMPs and TIMPs may be involved in the pathogenesis of bronchial asthma, and that the increased MMP-9 might be involved in the development of attack in patients with chronic asthma.     

Serum interleukin 6 (il-6A) concentration correlates with matrix metalloproteinases and their tissue inhibitors in rheumatoid arthritis

We explored whether the serum concentration of interleukin 6 (IL-6) is associated with matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in rheumatoid arthritis (RA) patients. Serum levels of IL-6, interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were assessed with an ELISA technique in 30 RA patients. We observed the association between IL-6 and MMP-1 (p < 0.001), MMP-3 (p < 0.05), MMP-9 (p < 0.001), TIMP-1 (p < 0.01) and TIMP-2 (p < 0.05). Additionally, serum IL-6, measured MMPs and TIMP-1 correlated with the erythrocyte sedimentation rate, C reactive protein plasma level and the number of swollen joints. We suggest that assessing the serum IL-6, MMP-1, MMP-3, MMP-9 and TIMP-1 levels may be helpful in the prediction of the RA activity.     

Lymphoid tissue collagen deposition in HIV-infected patients correlates with the imbalance between matrix metalloproteinases and their inhibitors

We studied the lymphoid tissue biopsies of 20 patients with chronic human immunodeficiency virus (HIV) infection by analyzing collagen deposition, CD4+ cell number, and gene expression of metalloproteinases (MMPs; MMP-2, MMP-9) and tissue inhibitors of MMPs (TIMPs; TIMP-1, TIMP-2). HIV-infected patients had significantly increased collagen deposition (P = .001), fewer CD4+ T cells (P = .05), and decreased MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios (P = .01), compared with HIV-negative control patients. Moreover, we found a significant negative correlation between collagen deposition and the MMP-9/TIMP-1 ratio (ρ = -0.50; P = .047). To our knowledge, this is the first time that MMP/TIMP imbalance has been correlated with lymphoid tissue collagen deposition and incomplete immune recovery in HIV-infected patients, even after long-term antiretroviral treatment.     

Associations of matrix metalloproteinase-9 and monocyte chemoattractant protein-1 concentrations with carotid atherosclerosis,based on measurements of plaque and intima–media thickness

Purpose

To examine associations of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-1 (MCP-1) concentrations with the severity of carotid atherosclerosis, based on measurements of carotid plaque and intima–media thickness (IMT).

Methods

This cross-sectional study included 116 stroke-free participants (45.7% males, 54.3% females; mean age, 64.73 ± 14.53 years). Serum MMP-9 and MCP-1 concentrations were measured, and plaque morphology, including total plaque score (PS), plaque stability, and IMT, was assessed ultrasonographically. Participants were grouped according to total PS (0, 1–2, ≥3), plaque stability (no plaque, stable, unstable) and IMT tertiles (<0.8 mm, 0.8–1 mm, >1 mm). Multinomial logistic regression models were used to assess the associations of MMP-9 and MCP-1 concentrations with plaque and IMT values after adjusting for vascular risk factors.

Results

MMP-9 quartiles (vs. quartile 1) were significantly associated with a greater prevalence of plaque instability [Q2: odds ratio (OR) = 5.13, 95% confidence interval (CI) = 1.01–24.9, p = 0.042; Q3: OR = 15.5, 95% CI = 3.1–78.1, p = 0.001; Q4: OR = 13.2, 95% CI = 2.7–64.97, p = 0.001] and high total PS (Q3: OR = 10.02, 95% CI = 1.5–65.33, p = 0.016; Q4: OR = 21.5, 95% CI = 3.5–132.1, p = 0.001). MCP-1 concentration was significantly associated with IMT (OR = 22.94, 95% CI = 2.14–245.66, p = 0.01).

Conclusions

Elevated serum MMP-9 concentration was independently associated with high total carotid artery PS, plaque instability, and large IMT value. MCP-1 concentration was independently associated with IMT, but not with plaque morphology.     

Serum MMP-9 Diagnostics,Prognostics, and Activation in Acute Coronary Syndrome and Its Recurrence

Matrix metalloproteinase (MMP)-9 is crucial in atherosclerotic plaque rupture and tissue remodeling after a cardiac event. The balance between MMP-9 and endogenous inhibitor, tissue inhibitors of matrix metalloproteinase 1 (TIMP-1), is important in acute coronary syndrome (ACS). This is an age- and gender-matched case-control study of ACS (N?=?669). Patients (45.7%) were resampled after recovery, and all were followed up for 6 years. The molecular forms of MMP-9 were investigated by gelatin zymography. Diagnostically, MMP-9 and the MMP-9/TIMP-1 molar ratio were associated with ACS (OR 5.81, 95% CI 2.65–12.76, and 4.96, 2.37–10.38). The MMP-9 concentrations decreased 49% during recovery (p?<?0.001). The largest decrease of these biomarkers between acute and recovery phase (ΔMMP-9) protected the patients from major adverse cardiac events, especially the non-fatal events. The fatal events were associated with in vitro activatable MMP-9 levels (p?=?0.028). Serum MMP-9 and the MMP-9/TIMP-1 molar ratio may be valuable in ACS diagnosis and prognosis. High serum MMP-9 activation potential is associated with poor cardiovascular outcome.     

Matrix-metalloproteinases and their inhibitors are elevated in severe sepsis: prognostic value of TIMP-1 in severe sepsis

The enzyme group of matrix metalloproteinases (MMPs) and their inhibitors, so-called tissue inhibitors of matrix-metalloproteinases (TIMPs), are crucial mediators responsible for wound repair after parenchymal damage. Little is known about the role of MMPs and TIMPs in severe sepsis. The aim of the present study was therefore to investigate their levels in patients with severe sepsis and to examine their association with prognosis. MMP-2, MMP-9, TIMP-1, TIMP-2 and interleukin-6 (IL-6) plasma levels were measured by ELISA methods in 37 patients on day 1 of severe sepsis. 37 healthy volunteers served as controls. Levels of MMP-9, TIMP-1, TIMP-2 and IL-6 in septic patients were significantly higher compared to healthy controls (p<0.001), whereas MMP-2 levels were not different in patients and controls. TIMP-1 levels were significantly higher in non-survivors (4675+/-435 ng/ml, mean+/-SEM) compared to survivors of severe sepsis (3201+/-249 ng/ml; p<0.01). Septic patients with TIMP-1 values >3200 ng/ml were 4.5 times more likely to die than patients with lower values (RR = 4.5; 95% CI 1.14-17.6, p = 0.014). Our results indicate that MMP-9, TIMP-2 and TIMP-1 are elevated in severe sepsis. Furthermore, TIMP-1 may serve as a useful laboratory marker to predict the clinical outcome of patients presenting with severe sepsis.     

Relationship of Matrix Metalloproteinases 2 and 9 in the Wall of Abdominal Aortic Aneurysms

This study examines the pathogenesis of abdominal aortic aneurysms (AAAs) with respect to pathological characteristics and expressions of matrix metalloproteinases (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1, in Tottori University Hospital, Japan. Thirty-four consecutive patients were operated on for (AAAs). During surgery, the anterior wall of the aneurysmal aorta was resected from the site of maximal diameter throughout the wall. AAA specimens consisted of the aneurysmal aortas, while control specimens consisted of the undulated aortas of autopsy cases. The expression of MMP-2, MMP-9 and TIMP-1 was evaluated by immunohistochemistry, Western blotting and competitive polymerase chain reaction (C-PCR). Immunohistochemistry showed MMP-2-positive cells and TIMP-1 positive cells mainly in the intima, and MMP-9-positive cells in the intima and adventitia. Western blotting revealed the expression of MMPs and TIMP-l variably in all the cases examined. C-PCR showed significantly higher elevation of MMP-2 mRNA in the small-diameter AAAs (30–45 mm), plus higher MMP-9 mRNA expression in both the small-diameter and the medium-large-diameter AAAs (45 < mm), than in controls. The ratio of MMP-2 to TIMP-1 mRNA levels in the small-diameter AAAs, and the ratio of MMP-9 to TIMP-1 mRNA levels in both the small-diameter and medium-large-diameter AAAs were significantly higher than in controls. The mRNA levels were significantly correlated between MMP-2 and MMP-9, between MMP-2 and TIMP-1, and between MMP-9 and TIMP-1 in the AAAs. This study demonstrates that increases in mRNA imbalanced expression of MMPs/TIMP, as well as increases of MMP-2 and MMP-9 expression, may play crucial roles in the development and growth of AAAs, and TIMP-1 may play an important rule of preventing the aortic expansion.     

Soluble CD40 ligand,interleukin (IL)-6, and hemostatic parameters in metabolic syndrome patients with and without overt ischemic heart disease

Background and aimSoluble CD40 ligand (sCD40L, also known as CD154) is a marker for platelet activation which could increase coagulation and inflammation. In this case-control study, we aimed to assess the levels of plasma sCD40L, IL-6, and some hemostatic parameters in patients with metabolic syndrome (MetS) whether or not associated with overt ischemic heart disease (IHD).Subjects and methodsWe measured plasma sCD40L (an index of platelet activation), interleukin (IL)-6 (a proinflammatory cytokine), and some hemostatic parameters (tissue factor [TF], thrombin–antithrombin [TAT] and D-dimer) in 47 patients with metabolic syndrome (21 with and 26 without overt IHD) versus 25 comparable healthy control subjects.ResultsSignificantly higher levels of sCD40L, IL-6, and thrombotic markers (TF, D-dimer and TAT) were found in patients with metabolic syndrome compared to healthy controls. The levels of IL-6 and sCD40 were highest in patients with overt IHD. Strong positive correlations existed between sCD40L and IL-6 (r = 0.67, p = 0.003), TF (r = 0.59, p = 0.008), and platelets count (r = 0.64, p = 0.005).ConclusionHigher levels of sCD40L, IL-6, and thrombotic markers exist in MetS patients, particularly those with IHD. The strong positive correlations between sCD40L and IL-6, TF, and platelets count support a link between the CD40–CD40L system and the underlying inflammatory and hypercoagulable state in MetS patients.     

Differing Expression of Cytokines and Tumor Markers in Combined Pulmonary Fibrosis and Emphysema Compared to Emphysema and Pulmonary Fibrosis

This study aimed to explore the different pathogeneses of combined pulmonary fibrosis and emphysema (CPFE) from emphysema and pulmonary fibrosis. The levels of transforming growth factor-β₁ (TGF-β₁), vascular endothelial growth factor (VEGF), Krebs Von Den Lungen-6 (KL-6), matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinases-1 (TIMP-1), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC), and the telomerase activity in peripheral blood were measured in 38 CPFE patients, 50 pulmonary emphysema patients, and 34 idiopathic pulmonary fibrosis (IPF) patients. The results demonstrated that the levels of VEGF and TGF-β₁ in IPF patients were significantly higher than those in emphysema patients (p < 0.05), and no significant differences were detected between CPFE patients and other two groups (p > 0.05). The levels of KL-6 and CYFRA21-1 in IPF patients were significantly higher than those in emphysema and CPFE patients (p < 0.05), and the latter had the similar levels (p > 0.05). Among the three groups, the levels of SCC, MMP-9, TIMP-1, MMP-9/TIMP-1 ratio, and telomerase activity were not different (p > 0.05). Our study showed that VEGF, TGF-β₁, KL-6, and CYFRA21-1 may play a role in the pathogenesis of pulmonary fibrosis. The lower levels of KL-6 and CYFRA21-1 in CPFE patients may be one of the reasons why these patients develop emphysema on the basis of fibrosis.