Levels Of Monocyte Chemoattractant Protein-1 In Patients Research Articles

Circulating Monocyte Chemoattractant Protein-1 in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction Treated with Mild Hypothermia: A Biomarker Substudy of SHOCK-COOL Trial

Background: There is evidence that monocyte chemoattractant protein-1 (MCP-1) levels reflect the intensity of the inflammatory response in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) and have a predictive value for clinical outcomes. However, little is known about the effect of mild therapeutic hypothermia (MTH) on the inflammatory response in patients with CS complicating AMI. Therefore, we conducted a biomarker study to investigate the effect of MTH on MCP-1 levels in patients with CS complicating AMI. Methods: In the randomized mild hypothermia in cardiogenic shock (SHOCK-COOL) trial, 40 patients with CS complicating AMI were enrolled and assigned to MTH (33 °C) for 24 h or normothermia at a 1:1 ratio. Blood samples were collected at predefined time points at the day of admission/day 1, day 2 and day 3. Differences in MCP-1 levels between and within the MTH and normothermia groups were assessed. Additionally, the association of MCP-1 levels with the risk of all-cause mortality at 30 days was analyzed. Missing data were accounted for by multiple imputation as sensitivity analyses. Results: There were differences in MCP-1 levels over time between patients in MTH and normothermia groups (P for interaction = 0.013). MCP-1 levels on day 3 were higher than on day 1 in the MTH group (day 1 vs day 3: 21.2 [interquartile range, 0.25–79.9] vs. 125.7 [interquartile range, 87.3–165.4] pg/mL; p = 0.006) and higher than in the normothermia group at day 3 (MTH 125.7 [interquartile range, 87.3–165.4] vs. normothermia 12.3 [interquartile range, 0–63.9] pg/mL; p = 0.011). Irrespective of therapy, patients with higher levels of MCP-1 at hospitalization tended to have a decreased risk of all-cause mortality at 30 days (HR, 2.61; 95% CI 0.997–6.83; p = 0.051). Conclusions: The cooling phase of MTH had no significant effect on MCP-1 levels in patients with CS complicating AMI compared to normothermic control, whereas MCP-1 levels significantly increased after rewarming. Trial registration: NCT01890317.

Monocyte chemoattractant protein-1 serum levels in depending on history of percutaneous coronary intervention in patients with coronary artery disease with type 2 diabetes mellitus

Background and Aims : Monocyte chemoattractant protein-1 (MCP-1) is a proinflammatory chemokine, which plays a key role in the pathophysiology of both atherosclerosis and diabetes. MCP-1 is involved in the development of neoatherosclerosis after percutaneous coronary intervention (PCI). Investigate serum MCP-1 levels in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) depending on the previous history of PCI.

Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in osteosarcoma

BackgroundOsteosarcoma is generally reported among younger individuals and has a very poor prognosis, particularly for the development of metastasis. However, more effective metastatic biomarkers and therapeutic methods are absent. Monocyte chemoattractant protein-1 (MCP-1) is involved in cancer progression and inflammatory recruitment. Although previous studies have reported higher serum MCP-1 levels in patients with osteosarcoma, the role of MCP-1 in osteosarcoma progression remains to be addressed.MethodsThe osteosarcoma cell migratory ability was assessed by transwell migration assay. The MCP-1 and MMP-9 expression levels were analyzed by Western blot and qPCR. The signal activation was conducted by Western blot. The in vivo mouse experiment and tumor tissue array were performed to confirm our findings in vitro.ResultsThe present study demonstrates that MCP-1 regulates cell mobility through matrix metalloproteinase (MMP)-9 expression in osteosarcoma cells. Moreover, MCP-1 promotes MMP-9 expression, cell migration, and cell invasion by mediating CCR2, c-Raf, MAPK, and AP-1 signal transduction. Using MCP-1 knockdown stable cell lines, we found that MCP-1 knockdown reduces MMP-9 expression and cell mobility. Finally, we found high MCP-1 expression levels in osteosarcoma specimens.ConclusionsOur results provide prognostic value of MCP-1 in osteosarcoma by promoting MMP-9 expression.

Serum malondialdehyde, monocyte chemoattractant protein-1, and vitamin C levels in wet type age-related macular degeneration patients.

Purpose:The purpose of this study was to investigate the serum levels of malondialdehyde (MDA) which is a marker of oxidative stress, monocyte chemoattractant protein-1 (MCP-1) which has an important role in inflammation, and vitamin C which has antioxidant properties in patients with wet age-related macular degeneration (wAMD).Methods:Thirty patients with wAMD were included in the study and serum levels of MDA, MCP-1, and vitamin C were compared with healthy participants (n = 30). Serum vitamin C and MDA levels were measured using a spectrophotometric method. Serum MCP-1 levels were determined by the ELISA method.Results:MCP-1 and MDA levels were higher in patients with wAMD compared with the control group (p < 0.05). Serum vitamin C levels were lower in patients with wAMD compared with the control group (p < 0.05).Conclusions:The increase in the MCP-1 levels in patients with wAMD may be associated with increased inflammation in wAMD. Decreased serum vitamin C and elevated MDA levels in patients with wAMD suggest increased oxidative stress in wAMD patients. These results indicate that the increased oxidative stress and inflammation can play a role in the pathogenesis of wAMD.

Effects of vitamin D supplementation on circulatory YKL-40 and MCP-1 biomarkers associated with vascular diabetic complications: A randomized, placebo-controlled, double-blind clinical trial

AimDiabetic patients predispose to vascular diseases such as nephropathy, and retinopathy. Poor adherence to medical treatment and dietary recommendations in uncontrolled diabetes leads to vascular damages. Vitamin D has been extensively studied and found to be protective against diabetes mellitus. YKL-40 and Monocyte chemoattractant protein-1 (MCP-1) are considered to exert crucial role in diabetes and its complications. Therefore, this study was designed to investigate effects of vitamin D supplementation on serum levels of YKL-40 and MCP-1 involved in the development of diabetic complications. MethodsFor 12 weeks, 48 type 2 diabetic patients enrolled in the trial and randomly were divided into two groups (n = 24 per group), receiving one of the following: 100 μg (4000 IU) vitamin D or placebo. Before and after intervention, serumYKL-40, MCP-1, insulin, IL-6, TNF-α, 25- (OH) vitamin D and HbA1c were measured. ResultsOur results revealed that serum levels of 25 (OH) vitamin D significantly increased in vitamin D group (p < 0.001). Vitamin D supplementation also significantly reduced serum YKL-40 levels (−22.7 vs. −2.4 ng/ml; (p-value = 0.003)). There was a significant decline in MCP-1 concentration in intervention group at the end of the study (−45.7 vs. −0.9 pg/ml; (p = 0.001)). Furthermore, there was a significant decrease in IL-6, fasting insulin and HOMA-IR in intervention group after 3 months supplementation. ConclusionsDaily vitamin D supplementation effectively reduced circulatory YKL-40 and MCP-1 levels in patients with type-2 diabetes and vitamin D deficiency. Vitamin D might contribute in reducing diabetic complications via modulating YKL-40 and MCP-1 signaling pathways.

Characterisation of urinary monocyte chemoattractant protein 1: Potential biomarker for patients with overactive bladder

ABSTRACTObjective: To investigate urinary monocyte chemoattractant protein 1 (MCP-1) as a potential marker for idiopathic overactive bladder (OAB). This is a quantitative measurement of urinary MCP-1 to establish baseline normal values that could help in future index studies. Normalised urinary MCP-1 levels are measured in female patients with OAB and aged-matched controls. Severity of OAB symptoms is correlated to normalised urinary MCP-1 levels.Patients and methods: Urinary MCP-1 levels were measured in 29 female patients with OAB and 10 normal female controls. The patients with OAB were either newly diagnosed or off any OAB oral therapy for at least 2 weeks. OAB symptoms were assessed using validated OAB questionnaires. Urinary MCP-1 levels were measured using enzyme-linked immunosorbent assay and normalised by urinary creatinine (Cr) levels.Results: The baseline urinary MCP-1 levels in female patients with OAB were significantly higher than those of the controls, at a mean of 210.25 vs 48.02 pg/mg Cr (P < 0.001). Patients who had severe OAB bother symptoms had higher levels of urinary MCP-1 (r = 0.03), also patients with OAB-wet had higher levels of urinary MCP-1, at a mean (SEM) of 209.25 (30.5) vs OAB-dry 185.25 (10) pg/mg Cr (P < 0.001).Conclusion: Urinary MCP-1 levels were higher in female patients with idiopathic OAB. The close association of urinary MCP-1 and OAB bother severity symptoms and OAB-wet suggest that inflammation plays a major role in the pathophysiological mechanisms underlying the sensitisation of bladder afferent nerves. Establishing urinary MCP-1 levels in patients with OAB hopefully will help future studies to confirm the correlation as a baseline and changes with treatments.Abbreviations: BMI: body mass index; Cr: creatinine; MCP-1: monocyte chemoattractant protein 1; OAB: overactive bladder; OAB-q: Overactive Bladder Questionnaire; PPBC: Patient Perception of Bladder Condition; UI: urinary incontinence

MCP-1 Levels are Associated with Cardiac Remodeling but not with Resistant Hypertension.

BackgroundHypertension is a chronic, low-grade inflammation process associated with the release of cytokines and development of target organ damage. Deregulated monocyte chemoattractant protein-1 (MCP-1) levels have been associated with high blood pressure and cardiovascular complications; however, the mechanisms involved are complex and not fully understood.ObjectiveThis study aimed to compare the levels of MCP-1 in patients with resistant (RH) versus mild-to-moderate (HTN) hypertension and their association with the presence or absence of left ventricular hypertrophy (LVH) in all hypertensive subjects.MethodsWe enrolled 256 hypertensive subjects: 120 RH and 136 HTN, investigating the relationship between circulating MCP-1 levels and blood pressure, biochemical data, hematologic profile, and cardiac damage within the RH and HTN groups. Plasma MCP-1 levels were measured by ELISA and LVH was assessed by echocardiography.ResultsWe found no difference in MCP-1 levels between RH and HTN subjects. On the other hand, we encountered lower MCP-1 levels in patients with LVH (105 pg/mL [100 - 260 pg/mL] versus 136 pg/mL (100 - 200 pg/mL), p = 0.005, respectively] compared with those without LVH. A logistic regression model adjusted for body mass index (BMI), age, race, aldosterone levels, and presence of diabetes and RH demonstrated that median levels of MCP-1 (2.55 pg/mL [1.22 - 5.2 pg/mL], p = 0.01) were independently associated with LVH in the entire hypertensive population.ConclusionSince MCP-1 levels were similar in both RH and HTN subjects and decreased in hypertensive patients with existing LVH, our study suggests a possible downregulation in MCP-1 levels in hypertensive individuals with LVH, regardless of hypertension strata.

Serum Levels of Monocyte Chemoattractant Protein-1 Correlate with Poor Clinical Grades in Cerebral Aneurysms.

Ruptured cerebral aneurysms (ICAs) are the most common non-traumatic cause of subarachnoid hemorrhage (SAH) that is associated with life threatening complications such as Vasospasm, Infarction, and Hydrocephalus (HCP). The active participation of macrophage/monocyte-mediated inflammatory response in the pathogenesis of cerebral aneurysm as labeled with Monocyte Chemoattractant Protein-1 (MCP-1) is suggested. To measure the serum level of MCP-1 in ruptured CAs in different time intervals. We measured the serum levels of MCP-1 in SAH patients who had CAs and compared it with that of MCP-1 in two control groups: including patients with SAH without CAs, and the normal population of blood donors. We also measured the MCP-1 levels in patients with CAs one week afterward to evaluate the effect of treatment. Serum level of MCP-1 was measured by a commercial ELISA assay. Mean serum MCP-1 level in patients with SAH and CAs was 188.2168 Pg/ml and 331.3982 Pg/ml in the normal population. There was no statistically significant difference between serum levels of MCP-1 on the first (mean=188.2168 Pg/ml) and 7th days after SAH onset (mean=171.8450 Pg/ml) (p=0.739). Serum level of MCP-1 increased significantly as Glasgow Coma Scale decreased (p=0.078) and Hunt and Hess score increased (p=0.089). Our results did not show an increasing MCP-1 serum level in patients with aneurysmal SAH. There was a relationship between poor clinical grade and MCP-1 levels in patients with CAs. MCP-1 may be a local inflammatory marker for cerebral aneurysms without systemic manifestation.

Association of monocyte chemoattractant protein 1 (MCP-1) gene polymorphism with lupus nephritis in Egyptian patients

Background and study aimMonocyte chemoattractant protein-1 (MCP-1) is a member of CC chemokine that plays an important role in the recruitment of monocytes/macrophages into renal tubulointerstitium. A biallelic A/G polymorphism at position ∼2518 in the MCP-1 gene was found to regulate MCP-1 expression. MCP-1 and its A/G gene polymorphism have been implicated in the pathogenesis of some renal diseases. The aim of the study was to investigate the role of the MCP-1 gene polymorphism as early predictors of the development of glomerulonephropathy in SLE patients. We also aimed to measure the serum and urinary levels of MCP-1 in patients with SLE, to find out its relation to clinical disease activity. Methods140 SLE patients (100 with nephritis and 40 without nephritis) and 80 controls were included in this study. MCP-1 gene polymorphism was analyzed by polymerase chain reaction. Serum and urine MCP-1 level were measured using high-sensitivity enzyme-linked immunosorbent assay. ResultsThe A/A genotype was more common in controls than in SLE patients, whereas both the A/G (P<0.000) and G/G (P<0.000) genotypes were more frequent in SLE patients. Carriers of G allele of the MCP-1 ∼2518 polymorphism had more than 7 fold increased risk to develop glomerulo-nephropathy in patients with SLE. High MCP-1 circulating levels production from patients with A/G and G/G genotypes was significantly higher than in A/A genotype. In addition there were significant differences in the mean levels of serum MCP-1 (P<0.001) and urinary MCP-1 (P<0.001) between patients and controls. ConclusionThe present study provides a new evidence that the presence of MCP-1 A (-2518) G gene polymorphism and high circulating MCP-1 levels can play an important role in the development of SLE and nephropathy in Egyptians.

Over-dialysis plasma RANTES increase depends on heparin dose and cardiovascular disease status

The lifespan of maintenance hemodialysis patients is reduced mainly because of cardiovascular complications due to accelerated atherosclerosis and impaired angiogenesis. We aimed to compare the effect of unfractionated heparin (UFH) and enoxaparin used as anticoagulants during hemodialysis (HD) on circulating levels of heparin-binding, anti-angiogenic Endostatin, pro-inflammatory RANTES (Regulated upon Activation, Normal T cell Expressed and Secreted), and MCP-1 (Monocyte Chemoattractant Protein-1). We enrolled 22 chronic HD patients, who were randomly assigned to either enoxaparin (n=11) or UFH (n=11) anticoagulation, and followed prospectively for 12 weeks before crossing over to the alternate therapy for further 12 weeks. The factors were measured (ELISA) at the start, 10 and 180 min of HD, and compared to 20 healthy volunteers. The baseline Endostatin, RANTES, and MCP-1 levels in patients were higher than in controls and comparable during enoxaparin and UFH treatment. RANTES significantly increased during both enoxaparin and UFH anticoagulated HD, while over-HD Endostatin and MCP-1 levels remained stable regardless of the heparin sort. About 25% RANTES increase after 10 min of HD positively correlated with the dose of both heparins and HD duration. The switch from enoxaparin to UFH treatment had no impact on the levels of parameters studied. Patients with ischemic heart disease had less RANTES increase after 180 min of HD especially during enoxaparin treatment. RANTES is dose-depended and transitory increased in response to both UFH and enoxaparin administration during HD. Cardiovascular disease status occurred to be the most important predictor of its over-HD level.

Levels of certain endothelial biomarkers during the acute phase and convalescence in patients with different severity of mediterranean spotted fever

Mediterranean spotted fever (MSF) is a tick-borne disease caused by Rickettsia conorii subspp. conorii. It is transmitted by the bite of the tick Rhipicephalus sanguineus. Modified by the rickettsial invasion, the micro-vascular endothelium acquires an activated inflammatory phenotype and initiates secretion of cytokines and expression of cell adhesion molecules (CAMs) and chemoattractans. This study aims at investigating the alterations in the soluble cellular adhesion molecules (sCAMs) and chemokine MCP-1 levels in patients with MSF of varying severity in the acute and convalescence stage in order to assess their diagnostic and prognostic value. The soluble forms of cellular adhesion molecules (sCAMs)--sE-selectin and sP-selectin, the intercellular (sICAM-1) and vascular (sVCAM-1) adhesion molecules as well as the monocyte chemoattractant protein-1 (MCP-1) were studied in the sera of 80 patients with MSF. The presence of MSF was confirmed serologically by indirect fluorescence assay (IFA). In order to study disease dynamics, serum samples from 80 patients were drawn on day 1 following the onset of rash; in 60 patients (part of the surveyed 80) a second sample was taken in the convalescence period--14 days post hospital discharge. The investigation was focused on mild, moderate and severe forms of MSF. Enzyme linked immune-sorbent assay was used for sCAMs determination (Quantikine IVD colorimetric Overall, in the acute stage, patients presented with increased levels of sE-selectin, sICAM-1, sVCAM-1 and MCP-1, whereas sP-selectin level was decreased. The levels of sE-selectin, sICAM-1 and sVCAM-1 were significantly elevated in mild, moderate and severe forms of the disease with sE-selectin level exhibiting a plateau tendency and sICAM and sVCAM levels demonstrating an upward trend from mild towards severe MSF forms. MCP-1 level was elevated only in severe MSF. In all forms of MSF, in the convalescence period, sICAM-1, sVCAM-1 and MCP-1 concentration returned to reference levels whereas sE-selectin level persisted elevated. In the convalescence stage, sP- selectin concentration also showed an upward tendency, which in severe forms of MSF slightly exceeded the level in controls. sP-selectin levels correlated directly with platelet count, whereas sICAM-1 and sVCAM-1 levels showed a reverse correlation, sE-selectin, sICAM-1 and MCP-1 levels directly correlated with aminotransferase activity (ALT and/or AST). The soluble forms of CAMs reflect the endothelial inflammatory potential. There is evidence that endothelium activation is more potent in severe forms of MSF. Assessment of the endothelial response in the course of the disease is an important predictor of the outcome, the choice of therapeutic approach and disease prognosis.

Monocyte chemoattractant protein-1 in schizophrenia: −2518A/G genetic variant and protein levels in Armenian population

Monocyte chemoattractant protein-1 (MCP-1) has been proposed as a contributory factor in pathophysiology of schizophrenia. The aim of the current study was to explore the possible association of the MCP-1−2518A/G genetic polymorphism and plasma levels of MCP-1 in patients with paranoid schizophrenia. The MCP-1−2518A/G (rs1024611) polymorphism and blood levels of MCP-1 in patients with paranoid schizophrenia and healthy subjects were evaluated and compared. One hundred and three chronic patients with paranoid schizophrenia treated with neuroleptics and 105 healthy subjects were genotyped using polymerase chain reaction with sequence-specific primers (PCR-SSP) and their MCP-1 plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay (ELISA). When comparisons were made between patients and controls, the frequency of the MCP-1−2518*G minor allele (35% vs 23%, p=0.009, OR=1.77, 95% CI: 1.1–2.04) and also of the MCP-1−2518*G carriers (60% vs 40%, p=0.003, OR=2.27, 95% CI: 1.13–2.01) were higher in patients. The mean value of the MCP-1 plasma level in patients with schizophrenia was significantly higher than in controls. Interestingly, the patients with the GG genotype had the highest MCP-1 level (711.4±211.4pg/ml), followed by those with the AG genotype (472.1±135.8pg/ml) and AA (372.4±180.2pg/ml) homozygotes. In conclusion, we report here the association of the −2518A/G genetic polymorphism and increased plasma levels of MCP-1 with schizophrenia and nominate −2518*G minor allele as a risk factor for schizophrenia in Armenian population.

The relation of serum monocyte chemoattractant protein-1 level with coronary atherosclerotic burden and collateral degree in stable coronary artery disease

We investigated whether serum monocyte chemoattractant protein-1 (MCP-1) level predicted coronary atherosclerotic burden in patients with stable coronary artery disease and its relationship with coronary collateral grade. We prospectively included 196 patients (103 males, 93 females; mean age 59 ± 11 years) who underwent coronary angiography for stable angina pectoris. Serum MCP-1 levels were determined before coronary angiography. Coronary atherosclerotic burden was measured by the Gensini score, and coronary collateral development was assessed by the Rentrop classification. The patients were divided into four groups: those with normal coronary arteries (NCA); those with coronary lesions of <70% luminal obstruction; and those with coronary lesions of ≥ 70% luminal obstruction accompanied by a good or poor collateral grade. The mean serum MCP-1 level was higher in patients with coronary lesions compared to patients with NCA (129 ± 130 vs. 102 ± 55 pg/ml, p=0.048). Although there were no significant differences in the MCP-1 levels of patients with NCA, with <70% luminal obstruction, and those with a significant luminal obstruction and a poor collateral grade, patients with significant luminal obstruction and a good collateral grade had significantly higher MCP-1 levels compared to the remaining groups (p=0.016). However, in multivariate regression analysis, MCP-1 level was not independently associated with the Gensini score. Our findings suggest that serum MCP-1 level is higher in patients with coronary atherosclerosis, without a significant and independent association with coronary atherosclerotic burden. Significantly increased serum MCP-1 levels in patients with a good collateral grade may be an interesting issue of investigation.

Increased monocyte chemoattractant protein-1 levels indicating early vascular damage in lean young PCOS patients

Serum levels of monocyte chemoattractant protein-1 and C-reactive protein levels, as early signs of vascular damage and cardiovascular disease, were increased in young, lean patients with polycystic ovary syndrome. Serum monocyte chemoattractant protein-1 levels were positively correlated with serum LH, T, and C-reactive protein levels.

Relationship between circulating levels of monocyte chemoattractant protein-1 and systolic dysfunction in patients with hypertrophic cardiomyopathy

Progression of hypertrophic cardiomyopathy (HCM) to left ventricular dilatation and systolic dysfunction sometimes occurs. However, the mechanism of the transition from hypertrophy to dysfunction has not been elucidated. It has been reported that circulating levels of monocyte chemoattractant protein-1 (MCP-1), which is a major factor promoting the accumulation of macrophages, are increased in patients with congestive heart failure. We measured circulating levels of MCP-1 in patients with HCM and examined whether MCP-1 was expressed in the myocardium of HCM patients. We also examined whether circulating levels of MCP-1 were correlated with left ventricular dysfunction. Circulating levels of MCP-1 were measured by an enzyme immunoassay in 26 patients with HCM (60+/-2 years old) and 20 control subjects (57+/-2 years old). Cardiac function was evaluated by two-dimensional echocardiography and cardiac catheterization. HCM patients had significantly elevated levels of MCP-1 (HCM: 309+/-30 vs. control: 178+/-8 pg/ml, P<.001). MCP-1 levels in patients with systolic dysfunction were significantly higher than those in patients without systolic dysfunction (P<.05) and were also significantly higher than those in patients with outflow obstruction (P<.05). Immunohistochemical analysis revealed that MCP-1 was expressed in endomyocardial biopsy samples obtained from HCM patients with systolic dysfunction. Furthermore, MCP-1 levels were inversely correlated with fractional shortening (r=-.401, P<.05) and correlated with left ventricular end-diastolic pressure (r=-.579, P<.01). These results show that MCP-1 is associated with, and might be involved in the pathogenesis of, left ventricular systolic dysfunction in patients with HCM.

Circulating advanced glycation end products (AGEs) and soluble form of receptor for AGEs (sRAGE) are independent determinants of serum monocyte chemoattractant protein‐1 (MCP‐1) levels in patients with type 2 diabetes

Atherosclerosis is an inflammatory disease. Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine responsible for the recruitment of monocytes to inflammatory lesions in the vasculature, an initial step of atherosclerosis. Since serum levels of MCP-1 are higher in patients with type 2 diabetes, inhibition of MCP-1 may be a novel therapeutic target for prevention of accelerated atherosclerosis in diabetes. However, little is known about the regulation and determinants of serum MCP-1 levels in patients with diabetes. In this study, we examined the determinants of serum MCP-1 levels in type 2 diabetic patients. Eighty-six consecutive outpatients with type 2 diabetes (36 male and 50 female; mean age 68.4+/-9.6) underwent a complete history and physical examination, determination of blood chemistries, MCP-1, tumour necrosis factor-alpha, adiponectin, advanced glycation end products (AGEs), and soluble form of receptor for AGEs (sRAGE). We examined the association between MCP-1 levels and those in anthropometric, metabolic and inflammatory variables in these subjects. Univariate regression analysis showed that serum levels of MCP-1 were positively associated with AGEs (r=0.386, p<0.001) and sRAGE (r=0.315, p<0.001). After adjusting for age and sex, AGEs (p<0.001) and sRAGE (p<0.05) still remained significant. The results demonstrate for the first time that circulating levels of AGEs and sRAGE are independent determinants of serum MCP-1 levels in patients with type 2 diabetes. Our present observations suggest the AGEs-RAGE system may be mainly involved in the elevation of MCP-1 in type 2 diabetic patients.

Elevated MCP‐1 serum levels are associated with the H63D mutation and not the C282Y mutation in hereditary hemochromatosis

Monocyte chemoattractant protein-1 (MCP-1) is a major lymphocyte and inflammatory chemokine associated with persistent inflammatory states. Several abnormalities in the immune status of patients with hereditary hemochromatosis (HH) have been reported, suggesting an imbalance in their immune function. This may include persistent production of, or exposure to, inflammatory cytokines contributing to the pathogenesis of this disorder. The aim of this study was to assess MCP-1 levels in patients with HH and correlate these results with HFE status and iron indexes. One hundred and thirty-nine subjects diagnosed with HH (C282Y homozygotes = 87, C282Y/H63D = 26 heterozygotes, H63D homozygotes = 26), 27 healthy control subjects with no HFE mutation (N/N), and 18 normal subjects heterozygous for the H63D mutation served as age- and sex-matched controls. Ferritin and transferrin saturation and the presence of HFE mutation status were correlated with MCP-1 levels. Full white blood cell count analysis was also performed. We found a strongly significant decrease in MCP-1 protein levels in the C282Y homozygotes compared with the H63D homozygotes (P = 0.0009) and C282Y/H63D heterozygotes (P = 0.002). Similarly, MCP-1 protein levels in the C282Y homozygotes were decreased compared with the healthy controls (P = 0.00076). Furthermore, MCP-1 serum levels were elevated in H63D patients compared with the healthy controls (P = 0.0008). This study suggests for the first time that a differential expression of MCP-1 protein in patients with HH is associated with the specific HFE genetic component for iron overload. Therefore, these findings offer a possible explanation in the variable clinical spectrum of pathogenesis in patients with HH through abnormalities of an imbalance in the immune states of patients with HH.

Effects of Long-Term Pravastatin Treatment on Serum and Urinary Monocyte Chemoattractant Protein-1 Levels and Renal Function in Type 2 Diabetic Patients with Normoalbuminuria

To explore the renoprotective and anti-inflammatory effects of pravastatin, we analyzed the changes in renal function and urinary monocyte chemoattractant protein-1 (MCP-1) level as a renal tubulointerstitial inflammatory biomarker and serum MCP-1 level as a systemic inflammatory biomarker following the introduction of treatment with 10 mg/day of pravastatin in 10 hyperlipidemic type 2 diabetic patients with normoalbuminuria. Twelve months of the pravastatin treatment did not affect urinary levels of albumin, transferrin, N-acetylglucosaminidase, or MCP-1 in the hyperlipidemic diabetic patients, whereas the treatment significantly reduced serum levels of MCP-1 in the patients. The pravastatin treatment effectively lowered low-density lipoprotein cholesterol (LDL-C) levels in the hyperlipidemic diabetic patients to levels nearly to those in 11 non-hyperlipidemic type 2 diabetic patients with normoalbuminuria. Interestingly, serum MCP-1 levels were significantly lower in the hyperlipidemic patients treated with pravastatin than in the non-hyperlipidemic patients. No significant correlation was observed between serum LDL-C and MCP-1 levels in all the data in the hyperlipidemic patients before and after the pravastatin treatment and in the non-hyperlipidemic patients. These results collectively indicate that pravastatin may ameliorate systemic vascular inflammation rather than local renal inflammation in hyperlipidemic type 2 diabetic patients with normoalbuminuria, independent of its cholesterol-lowering effects.

The Post-Operative Level of Serum Monocyte Chemoattractant Protein-1 and Its Correlation With the Severity of Surgical Stress

Several basic studies have demonstrated that monocyte chemoattractant protein-1 (MCP-1) influences type 2 cytokine production and cell-mediated immunity. However, there have been few reports on the changes in serum MCP-1 levels in patients undergoing major thoracoabdominal surgery. In this study, we examined the kinetics of serum MCP-1 post-operatively and clarified its significance regarding the extent of surgical stress. Seventeen patients who underwent surgical operations were included in this study. All of them were fed by total parenteral nutrition to deliver the same amount of calories and nitrogen. Of the severely stressed group, nine patients underwent esophagectomy with thoracotomy. Of the group of moderately stressed group, eight patients underwent gastric or colorectal surgery. Serum MCP-1 and interleukin-6 (IL-6) were measured after operation. Cell-mediated immunity was measured by concanavalin A- or phytohemagglutinin-stimulated lymphocyte proliferation on the seventh post-operative day. Serum MCP-1 and IL-6 were increased immediately after surgery in both groups. The level of MCP-1 was significantly higher in the group of severely stressed patients than in the moderately stressed group. Concanavalin A or phytohemagglutinin-stimulated lymphocyte proliferation was significantly lower in the severely stressed group than in the moderately stressed group. These results indicate that serum MCP-1 levels are directly correlated, and cell-mediated immunity inversely correlated, with the severity of surgical stress.

Intravenous prostaglandin E1 reduces monocyte chemoattractant protein-1 levels in peripheral arterial obstructive disease

Objectives Blood monocytes are the precursors of the lipid-laden foam cells that are the hallmark of early atherosclerotic lesions, and monocyte chemoattractant protein-1 (MCP-1) plays important roles in their recruitment to the vessel wall. In this study, we measured serum levels of MCP-1 in patients with peripheral arterial obstructive disease (PAOD) and investigated whether intravenous prostaglandin E1 (PGE1) treatment, which produces clinical benefits in PAOD, might decrease such levels. Methods Eight patients with PAOD at Fontaine stage II to IV were treated with a daily intravenous infusion of 10 μg of PGE1 for 7 consecutive days. Blood samples before and after 7-day PGE1 treatment were used for assays of MCP-1, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), von Willebrand factor (vWF), and endothelin-1 (ET-1). Results Serum MCP-1 levels in patients with PAOD were significantly higher than those in healthy control subjects (263.8 ± 52.8 vs 136.5 ± 15.0 pg/mL, P =.002). PGE1 administration for 7 days resulted in a significant decrease in the MCP-1 level, from 263.8 ± 52.8 to 196.1 ± 25.5 pg/mL (P =.02), whereas levels of IL-6, hs-CRP, and ET-1 and the activity of vWF were not affected. Conclusions Serum MCP-1 levels were elevated in patients with PAOD, indicating the involvement of activation of monocytes in the pathogenesis of this disorder. Parenteral administration of PGE1 appeared to decrease circulating MCP-1 levels, which might lead to the suppression of the development of atherosclerotic lesions in patients with PAOD. (Am Heart J 2003;145:330-3.)