Monocyte Chemoattractant Protein-1 Elevation Research Articles

The Role of Endothelial Barrier Function in the Fibrosis of Salivary Gland

In the salivary glands, fibrosis occurs in many pathological conditions. Endothelial tight junction (TJ)–based barrier function plays a vital role in maintaining the homeostasis of the salivary glands. However, whether endothelial barrier function is changed and involved in the pathogenesis of glandular fibrosis is unknown. Here, by using a mouse model in which the main excretory duct of the submandibular gland (SMG) was ligated to induce inflammation and fibrosis, endothelial barrier function and TJ protein expression and distribution were examined. Both 4-kDa and 70-kDa fluorescence-labeled dextrans permeated more in the 1-, 3-, and 7-d ligated SMGs. Meanwhile, the mRNA level of claudin-5 was increased with an obvious redistribution from apicolateral membranes to lateral membranes and cytoplasm in the fibrotic glands. Notably, the TJ sealer AT1001 significantly attenuated the disrupted endothelial barrier function and thereby ameliorated the glandular fibrosis. Cytokine array detection showed that monocyte chemoattractant protein–1 (MCP-1) was highly enriched in the 3-d ligated SMGs, and MCP-1 directly impaired barrier function, increased claudin-5 expression, induced the relocalization of claudin-5, and activated p-ERK1/2 in cultured human endothelial cells. Furthermore, the upregulation and disorganization of claudin-5 as well as the elevation of MCP-1 and p-ERK1/2 signaling were also confirmed in fibrotic SMGs from patients with chronic sialadenitis and immunoglobulin G4–related sialadenitis. Altogether, our findings revealed that disrupted endothelial barrier function contributed to the progression of glandular fibrosis, and targeting endothelial TJs might be a promising approach to alleviate salivary gland fibrosis-related diseases.

Early Monocyte Chemoattractant Protein-1 Elevation Predicts Surgical Site Infections after Blunt Trauma.

Background: Dysregulation of the inflammatory and immune response to injury may increase susceptibility to secondary infections after trauma. It is unknown whether cytokines involved in this response could function as plasma biomarkers for surgical site infection (SSI). We hypothesized that the early cytokine response differs between patients who develop SSI and those who do not and that critical cytokine threshold values could be used to predict risk of SSI. Patients and Methods: Using the Glue Grant database, we performed an analysis of severely injured blunt trauma patients who underwent a major procedure and had available cytokine data. Patients were divided into SSI and no SSI groups. Receiver operating curve analysis was used to determine acceptable early cytokine predictors of SSI and critical threshold values. Multivariable regression analysis was then performed to determine the odds of developing SSI using threshold values, adjusting for key patient or injury factors. Cytokine levels were compared between SSI and no SSI groups at three time points. Results: The study cohort consisted of 70 patients and 11 patients developed SSI. Monocyte chemoattractant protein-1 (MCP-1) was the only acceptable early predictor of SSI with an area under the curve (AUC) of 0.71 (p = 0.03) and a critical threshold value of 490 pg/mL. Monocyte chemoattractant protein-1 levels above this threshold within 24 hours of injury were associated with SSI (adjusted odds ratio [AOR] 8.1; p = 0.01). Monocyte chemoattractant protein-1 levels within 24 hours of injury were higher in those who developed SSI (994 vs. 259 pg/mL; p < 0.01) and remained higher in the SSI group at 33 hours from injury (338 vs. 144 pg/mL; p = 0.01), but were similar by 106 hours (155 vs. 97 pg/mL; p = 0.19). Conclusion: Among cytokines involved in the early response to trauma, only early elevation of MCP-1 predicted SSI after blunt trauma. Monocyte chemoattractant protein-1 may act as a specific and early marker for SSI after blunt trauma, allowing for preventative measures to mitigate risks.

Hemodynamic ,thyroid and immunomodulater effects of cannabinoid in rats.

The aims of the present study are to investigate the cannabinoid effects on serum&#x0D; monocyte chemoattractant protein-1 (MCP-1), Troponin-1 ,liver and renal test&#x0D; parameters. The experimental rats were divided into three groups, the first group served&#x0D; as a control, and the animals were injected with normal saline. In the second group,&#x0D; animals were injected with cannabis (5 mg/kg, intraperitonial), while in the third group&#x0D; animals were injected with cannabis (10 mg/kg). After the course of the experiment,&#x0D; systolic blood pressure (SBP) tended to reduce significantly in the second dose of&#x0D; cannabis administered rats. Serum nitric oxide (NO) level slightly increased in dose&#x0D; dependent manner but it did not reach the level of significance. Serum level of&#x0D; malondialdehyde (MDA), troponin-T, MCP-1 and serum total bilirubin were&#x0D; significantly increased in the second dose of cannabis administration as compared to&#x0D; control rats. Neither triiodothyronin (T3) nor tetraiodothyronin (T4) hormones had&#x0D; statistically changed in cannabis group comparing with the control rats. Furthermore,&#x0D; serum uric acid reduced in cannabis group as compared with control. In conclusions, for&#x0D; the first time, our findings suggested that cannabis could affect immune system through&#x0D; MCP-1 elevation. As well as, cannabis may affect cardiac and liver functions via&#x0D; increasing troponin-T and bilirubin levels.

English

Diacetylmorphine (heroin) has many effects on the body system; it exerts effects on cardiovascular, immune and endocrine systems. The aim of the this study is to investigate the short-term effects of low and high doses of heroin on systolic blood pressure (SBP), thyroid hormones and monocyte chemoattractant protein-1 (MCP-1). The experimental rats were divided into three groups, each with six individuals and the treatments were continued for seven days. SBP significantly reduced by heroin administration in the second dose as compared with the control group. A marked decrease in the serum NO level was also noticed after first (low) and second (high) dose of administration as compared with control group. The present results also revealed that serum MCP-1 was statistically increased in the second dose of heroin group. Statistical analysis showed that both serum T 3 and T 4 levels were reduced significantly by heroin administration. In conclusions, for the first time, our findings suggested that diacetylmorphine could affect immune system through MCP-1 elevation. As well as heroin may affect cardiac and liver functions via increasing troponin-T and bilirubin levels.

Intermittent hypoxia induces NF-κB-dependent endothelial activation via adipocyte-derived mediators.

Aberrant release of adipocytokines from adipose tissues dysregulates cardiometabolic functions. The present study hypothesizes that chronic intermittent hypoxia (IH) present in obstructive sleep apnea leads to adipose tissue dysfunction, which in turn contributes to vascular pathogenesis. The effect of IH was evaluated in adipose depots and aortic tissues in lean rats in vivo. Furthermore, the cellular and molecular mechanisms underlying pathophysiological interactions between adipocytes and endothelial cells were investigated in vitro. The in vivo results showed that IH induced upregulation of IL-6 and monocyte chemoattractant protein-1 (MCP-1) in subcutaneous and periaortic adipose tissues and downregulated phosphorylation of endothelial nitric oxide synthase [eNOS (ser1177)] in the aorta with activation of Erk and p38 MAPK. In support, cultured adipocytes demonstrated IH-induced elevations of NADPH oxidase 4, phosphorylation of Erk, NF-κBp65, and inducible NOS (iNOS) and increased expression of IL-6 and MCP-1. Likewise, endothelial EA.hy926 (EA) cells exposed to IH showed eNOS (ser1177) and intracellular cGMP reduction, whereas MCP-1 and iNOS expression were upregulated. Treatment of EA cells with conditioned media derived from IH-exposed cultured adipocytes caused nuclear translocation of NF-κBp65 and elevation of MCP-1, which were prevented by addition of neutralizing IL-6 antibodies to the conditioned media. Recombinant IL-6 in addition to IH induced further MCP-1 release and iNOS protein expression in EA cells, which were prevented by pharmacological inhibition of Erk, p38, and NF-κB. These findings suggest that IH could induce adipose tissue inflammation, which may cross talk with endothelial cells via adipocyte-derived mediators such as IL-6, and promote NF-κB-dependent endothelial dysfunction.

Association of inflammaging (inflammation + aging) with higher prevalence of OAB in elderly population

Although epidemiology studies consistently report increased prevalence of overactive bladder (OAB) with age, an accurate deciphering of causative links between the two entities remains elusive. Studies on aged rodent bladder have so far yielded contradictory results on age-associated changes in muscarinic receptors, which highlight the challenge posed by species differences in understanding OAB pathology. We hypothesized that age-related biochemical changes in bladder leading to altered bladder function will be reflected in altered urinary proteome of elderly OAB patients. Single time point urine specimens were obtained from 140 OAB patients in the age range of 25-90 years of either sex coming routinely to the urology clinics. Eight chemokines in urine were measured by MILLIPLEX MAP human cytokine/chemokine multiplex immunoassay and ELISA. Multivariate and univariate statistical analyses were done to determine association of age with urinary chemokines in OAB patients. In agreement with age-dependent higher prevalence of OAB, the logistic regression of the data also revealed the significant association of OAB symptoms with age [odds ratio (OR) 1.12; 95 % CI, (1.072, 1.187), p = 0.0001]. Univariate analysis of 8 urinary proteins revealed an age-associated elevation of NGF (nerve growth factor) in 137 out of 140 OAB patients [Pearson r = 0.274; 95 %CI (0.112-0.422); p = 0.001]. Modest correlation with age was also noted for MCP-1 (monocyte chemoattractant protein-1), which was detected in 115 OAB patients, and the remaining chemokines were undetectable in nearly two-third of OAB patients included in our cohort. Based on our findings, we postulate that age-associated biochemical changes may accentuate the inflammation associated with OAB. Urinary NGF elevation in elderly OAB patients may be a homeostatic response to counter the senescence of bladder nerves and arrest the progression of OAB into detrusor hyperactivity with impaired contractility. Likewise, elevation of MCP-1 may be related to decreased muscle mass and increased content of adipose tissue in bladder of elderly OAB patients. Urinary NGF and MCP-1 can serve as surrogate markers for monitoring age-associated biochemical changes and the effect of therapeutic interventions in OAB patients.

Identification of Serum Monocyte Chemoattractant Protein-1 and Prolactin as Potential Tumor Markers in Hepatocellular Carcinoma

Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed in HCC and are conveniently quantifiable in patients’ sera by ELISA. MCP-1 appears to be a promising complementary biomarker for HCC diagnosis and this MCP-1+AFP model should be further evaluated as potential biomarker on a larger scale in patients at-risk of HCC.

Antecedent acute kidney injury worsens subsequent endotoxin-induced lung inflammation in a two-hit mouse model

Acute kidney injury (AKI) contributes greatly to morbidity and mortality in critically ill adults and children. Patients with AKI who subsequently develop lung injury are known to suffer worse outcomes compared with patients with lung injury alone. Isolated experimental kidney ischemia alters distal lung water balance and capillary permeability, but the effects of such an aberration on subsequent lung injury are unknown. We present a clinically relevant two-hit murine model wherein a proximal AKI through bilateral renal ischemia (30 min) is followed by a subsequent acute lung injury (ALI) via intratracheal LPS endotoxin (50 μg at 24 h after surgery). Mice demonstrated AKI by elevation of serum creatinine and renal histopathological damage. Mice with ALI and preexisting AKI had increased lung neutrophilia in bronchoalveolar lavage fluid and by myeloperoxidase activity over Sham-ALI mice. Additionally, lung histopathological damage was greater in ALI mice with preexisting AKI than Sham-ALI mice. There was uniform elevation of monocyte chemoattractant protein-1 in kidney, serum, and lung tissue in animals with both AKI and ALI over those with either injury alone. The additive lung inflammation after ALI with antecedent AKI was abrogated in MCP-1-deficient mice. Taken together, our two-hit model demonstrates that kidney injury may prime the lung for a heightened inflammatory response to subsequent injury and MCP-1 may be involved in this model of kidney-lung cross talk. The model holds clinical relevance for patients at risk of lung injury after ischemic injury to the kidney.

Circulating levels of MCP‐1 are increased in women with gestational diabetes

We investigated whether gestational diabetes mellitus is associated with monocyte-chemoattractant-protein-1 (MCP-1) and soluble CD40 ligand (sCD40L), the functional relevant proteins in the inflammatory process. In all 32 women with gestational diabetes mellitus, 18 women without gestational diabetes mellitus and 40 nonpregnant women were included. MCP-1 and sCD40L were measured at the time of the oral glucose tolerance test (second trimester), in the third trimester and postpartum. MCP-1 was higher in pregnant women (women with gestational diabetes mellitus and without) than in nonpregnant women (p < 0.001) in the third trimester, and also in the second trimester and postpartum. MCP-1 was elevated in patients with gestational diabetes mellitus in the third trimester compared to healthy pregnant women (p = 0.007). In gestational diabetes mellitus, MCP-1 increased from the second to the third trimester (p = 0.003). We found no association of sCD40L and gestational diabetes mellitus. The elevation of MCP-1 in the third trimester in gestational diabetes mellitus suggests an association between inflammation and GDM.

Elevation of monocyte chemoattractant protein-1 in patients experiencing neurocognitive decline following carotid endarterectomy

Previous studies have demonstrated that elevated pre-operative monocyte count is an independent predictor of acute neurocognitive decline following carotid endarterectomy (CEA). Monocyte chemoattractant protein-1 (MCP-1), secreted by human endothelial and monocyte-like cells, is a potent mediator of inflammation and mononuclear cell trafficking. This study examines the relationship between peri-operative serum MCP-1 elevation and post-operative neurocognitive injury following CEA. Fifty-two patients undergoing CEA and 67 lumbar laminectomy (LL) controls were administered a battery of five neuropsychological tests pre-operatively and on post-operative day 1 (POD 1). Change in individual test scores from baseline to POD 1 were converted into Z-score and used to develop a point system quantifying the degree of neurocognitive dysfunction relative to change within the LL group. Neurocognitive injury following CEA was defined as a score greater than 2 standard deviations above mean total deficit scores of LL controls. Serum MCP-1 levels were measured pre-operatively and on POD 1 by enzyme-linked immunosorbent assay. Mean percent MCP-1 elevation was higher for the 13 injured CEA patients (147.7 +/- 32.4%) in our cohort compared to 39 age- and sex-matched uninjured CEA patients (76.0 +/- 16.5%). In unconditional multivariate logistic regression analysis, percent elevation in serum MCP-1 level was associated with neurocognitive injury one day after CEA (OR = 2.19, 95% CI = 1.13-4.26, P = 0.021, for a 100% elevation from pre-operative levels). Peri-operative elevations in serum MCP-1 levels correlate with acute neurocognitive dysfunction following CEA. These data implicate an inflammatory mechanism in the pathogenesis of Ischaemic neurocognitive decline.

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.

Overexpression of monocyte chemoattractant protein 1 in the brain exacerbates ischemic brain injury and is associated with recruitment of inflammatory cells.

Brain cells produce cytokines and chemokines during the inflammatory process after stroke both in animal models and in patients. Monocyte chemoattractant protein 1 (MCP-1), one of the proinflammatory chemokines, can attract monocytes to the tissue where MCP-1 is overexpressed. However, the role of MCP-1 elevation in stroke has not been explored in detail. The authors hypothesized that elevated MCP-1 levels would lead to increased influx of monocytes and increased brain infarction size in stroke induced by middle cerebral artery occlusion with partial reperfusion. There were no differences in blood pressure, blood flow, or vascular architecture between wild-type mice and transgenic MBP-JE mice. Twenty-four to 48 hours after middle cerebral artery occlusion, brain infarction volumes after ischemia were significantly larger in MBP-JE mice than in wild-type controls and were accompanied by increased local transmigration and perivascular accumulation of macrophages and neutrophils. These results indicate that MCP-1 can contribute to inflammatory injury in stroke.

CC-chemokine activation in acute pancreatitis: enhanced release of monocyte chemoattractant protein-1 in patients with local and systemic complications.

Systemic leukocyte activation is claimed to trigger inflammatory response and remote organ dysfunction in acute pancreatitis. Chemokines are inflammatory mediators with potent leukocyte-activating properties and have been shown to be involved in the pathophysiological process of experimental acute pancreatitis. However, as little is known about their role in human disease we investigated local and systemic concentrations of different CC-chemokine members in patients with acute pancreatitis. We included 68 patients with acute pancreatitis in the present study. Local complications in terms of necrosis were present in 37 (54%) patients of whom 21 (57%) developed pancreatic infections. Monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and macrophage inflammatory protein-1beta (MIP-1beta) concentrations were measured daily over 2 weeks after study inclusion by ELISA in sera and lesser sac aspirates. MCP-1 serum concentrations showed a dramatic increase in patients who developed local complications and/or remote organ failure. Herein, a close correlation was found between the severity of remote organ failure and the degree of MCP-1 elevation. Multiple regression analysis identified pancreatic infections as well as renal and cardiocirculatory failure as independent variables associated with enhanced systemic MCP-1 release. MIP-1alpha levels remained unaffected by local complications and showed a significant increase only; if multiple organ dysfunction syndrome (MODS) developed or patients subsequently died. In contrast, MIP-1beta concentrations correlated with neither the presence nor the severity of any complication. Compared with systemic concentrations, local lesser sac aspirates revealed significantly higher levels of MCP-1, whereas MIP-1alpha and MIP-1beta were not different. Complicated acute pancreatitis is associated with significantly elevated local and systemic concentrations of the CC-chemokine MCP-1. Our results suggest that, among the CC-chemokine members investigated, MCP-1 might play a pivotal role in the pathological mechanism of complicated acute pancreatitis.

In vitro Effects of Habu Snake Venom on Cultured Mesangial Cells

Background: Habu snake venom (HSV)-induced glomerulonephritis is a unique model showing a progressive course of mesangial proliferation. To elucidate the in vitro effects of HSV, we examined whether HSV itself could have direct effects on the cultured mesangial cells, such as cell proliferation and activation of chemokine gene expression. Methods: The incorporation of 5-[¹²⁵I]iodo-2’-deoxyuridine was measured with a γ-counter, and gene expressions of growth factors, chemokines and cytokines were evaluated by a real time quantitative PCR. Results: We demonstrated that excessive or continuous HSV stimulation decreased a mesangial cell viability. However, adequate and temporary HSV stimulation induced proliferation of mesangial cells in vitro along with a significant elevation of monocyte chemoattractant protein-1 (MCP-1) mRNA levels. In addition to these in vitro results, we showed that MCP-1 mRNA levels increased in renal cortices of glomerulonephritis induced by HSV. Immunohistochemistry also showed a positive staining for MCP-1 in the marginal area of glomerulus with mesangiolysis. Conclusions: These data suggest that HSV itself may elicit direct biological effects on mesangial cells which may participate in pathophysiology of glomerulonephritis induced by HSV.

Inflammation and intimal hyperplasia associated with experimental pulmonary embolism

Objective: We tested the hypothesis that a venous thromboembolism to the pulmonary arterial system (pulmonary embolism [PE]) would cause an inflammatory response within the pulmonary arterial (PA) wall marked by elevated cytokines and chemokines and an influx of inflammatory cells. Methods: Experimental PE was induced in 70 rats and confirmed with angiography and O 2 saturation depression, and an additional 70 rats underwent sham operations. PA and lung tissue were removed at 3 hours and at 1, 2, 4, 6, 8, and 14 days (n = 10 per time point), were analyzed for proinflammatory cytokines and chemokines, and underwent histologic analysis. Data were analyzed with analysis of variance and the unpaired Student t test. Results: Average gross PE resolution was 40% at 2 days, 90% at 4 days, and 100% at 6 days. Only monocyte chemoattractant protein-1 levels were greater in affected PAs compared with sham PAs at 3 hours, 1 day, and 2 days (137 ± 13 pg/mg protein, 285 ± 40 pg/mg protein, and 249 ± 36 pg/mg protein versus 101 ± 6 pg/mg protein, 150 ± 36 pg/mg protein, and 92 ± 3 pg/mg protein; P < .01 for all). Keratinocyte-derived chemokine, tissue necrosis factor, interleukin-10, nitric oxide, P-selectin, and E-selectin levels were not elevated. Neutrophils infiltrated the PA wall beginning at 3 hours, peaked at 2 days (69.4 ± 21.7 per five high-power fields; P < .01), and returned to baseline by 8 days after PE. Macrophages peaked at 1 day after PE (29.3 ± 6.9; P < .01) and returned to baseline by 4 days after PE. PE also was associated with a significantly increased intima to media ratio ( P < .05), apparent at 4 days after PE and persisting through 14 days. Conclusion: PE is associated with an early influx of polymorphonuclears and macrophages and monocyte chemoattractant protein-1 elevation within the PA wall. These are temporally associated with thrombus resolution and intimal hyperplasia. These factors may mediate these two processes after PE. This offers targets for further study with the hopes of minimizing the pathophysiologic response to PE. (J Vasc Surg 2002;36:581-8.)

Monocyte chemoattractant protein-1 in patients with peripheral arterial disease.

BACKGROUND: Chemokine-driven migration of inflammatory cells has been implicated in the pathogenesis of atherosclerotic conditions including peripheral arterial disease (PAD). Monocyte chemoattractant protein-1 (MCP-1) is elevated in patients with coronary artery disease and in hypertensive patients. This study therefore investigated MCP-1 in patients with PAD. METHODS: Serum MCP-1 was determined by enzyme-linked immunosorbent assay in 36 healthy, control subjects and in 19 patients with PAD. Statistical analysis utilised the Mann-Whitney test and Spearman correlation (p < 0.05). RESULTS: MCP-1 (pg/ml) was increased in patients compared with in controls (mean+/-standard error of the mean: PAD group, 748+/-60; control group, 459+/-27; p=0.0001). MCP-1 levels tended to decrease with progressing disease. From atherosclerosis risk factors, diabetes inclined to increase MCP-1 levels; hypertension had no effect. Serum MCP-1 correlated with cholesterol, triglycerides, low-density lipoprotein but not high-density lipoprotein. Conclusion: Elevation of MCP-1 in the circulation of PAD patients shown in the present pilot study implicates this CC chemokine ligand 2 in inflammatory processes contributing to PAD clinical symptomatology. Further investigations are necessary to evaluate whether MCP-1 can be used as a potential marker of peripheral arterial disease follow-up and/or prognosis.