Circulating mononuclear superoxide production and inflammatory markers for long-term prognosis in patients with cardiac syndrome X

Increased oxidative stress and vascular inflammation have been shown in patients with cardiac syndrome X (CSX; angina, exercise-induced ischemia, and normal coronary angiogram). This study was conducted to assess the impact of basal superoxide generation by circulating mononuclear cells (MNCs), a contributor to intravascular oxidative stress, and serum inflammatory biomarkers, including high-sensitivity C-reactive protein, homocysteine, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and von Willebrand factor, on the long-term prognosis of CSX. During a mean follow-up of 31.5 +/- 14.2 months (maximum 5 years), a total of 12 events were recorded in 92 consecutive CSX patients. There were no deaths or myocardial infarctions, but 8 hospitalizations for acute coronary syndrome, 3 for stroke, and 1 for congestive heart failure due to left ventricular systolic dysfunction. Under univariate analysis, only basal superoxide generation by MNCs was associated with the risk for cardiovascular event. Based on multivariate analysis, basal superoxide generation by MNCs could still independently predict future events (relative risk for the highest compared to the lowest tertile, 3.87; 95% confidence interval, 1.42-10.54, p = 0.008). These findings demonstrate that long-term prognosis is fair in patients with CSX. Basal superoxide production of MNCs independently predicts future cardiovascular events, suggesting its potential role in measuring disease progression and risk stratification in these patients.     

Early Vascular Alterations in SLE and RA Patients-A Step towards Understanding the Associated Cardiovascular Risk

Accelerated atherosclerosis represents a major problem in both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients, and endothelial damage is a key feature of atherogenesis. We aimed to assess early endothelial changes in SLE and RA female patients (127 SLE and 107 RA) without previous CV events. Biomarkers of endothelial cell activation (intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), thrombomodulin (TM), and tissue factor (TF)) were measured and endothelial function was assessed using peripheral artery tonometry. Reactive hyperemia index (RHI), an indicator of microvascular reactivity, and augmentation index (AIx), a measure of arterial stiffness, were obtained. In addition, traditional CV risk factors, disease activity and medication were determined. Women with SLE displayed higher sICAM-1 and TM and lower TF levels than women with RA (p?=?0.001, p<0.001 and p<0.001, respectively). These differences remained significant after controlling for CV risk factors and medication. Serum levels of vascular biomarkers were increased in active disease and a moderate correlation was observed between sVCAM-1 levels and lupus disease activity (rho?=?0.246) and between TF levels and RA disease activity (rho?=?0.301). Although RHI was similar across the groups, AIx was higher in lupus as compared to RA (p?=?0.04). Also in active SLE, a trend towards poorer vasodilation was observed (p?=?0.06). In conclusion, women with SLE and RA present with distinct patterns of endothelial cell activation biomarkers not explained by differences in traditional CV risk factors. Early vascular alterations are more pronounced in SLE which is in line with the higher CV risk of these patients.     

Effects of progressive and maximal exercise on plasma levels of adhesion molecules in athletes with sickle cell trait with or without alpha-thalassemia.

The aim of the study was to examine the effects of exercise on soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in sickle cell trait (SCT) athletes with or without alpha-thalassemia. Six athletes with SCT, seven athletes with both SCT and alpha-thalassemia (SCTAT), and seven control athletes (Cont) performed an incremental and maximal test on cycloergometer. Levels of sICAM-1 and sVCAM-1 were assessed at rest, immediately after the end of exercise, and 1, 2, and 24 h after exercise. Although Cont and SCTAT groups exhibited similar basal plasma levels of inflammatory and adhesion molecules, the SCT group had higher sVCAM-1 basal concentrations. Incremental exercise resulted in a significant increase of sVCAM-1 in all subjects, which remained elevated only in the SCT group during the recovery period. In conclusion, as sVCAM-1 increased with exercise and during the recovery period, our findings support the concept that SCT athletes might be at risk for microcirculatory disturbances and adhesive phenomena developing at rest and several hours after exercise. alpha-Thalassemia might be considered protective among exercising SCT subjects.     

VCAM-1 as a predictor biomarker in cardiovascular disease

The vascular cellular adhesion molecule-1 (VCAM-1) is a protein that canonically participates in the adhesion and transmigration of leukocytes to the interstitium during inflammation. VCAM-1 expression, together with soluble VCAM-1 (sVCAM-1) induced by the shedding of VCAM-1 by metalloproteinases, have been proposed as biomarkers in immunological diseases, cancer, autoimmune myocarditis, and as predictors of mortality and morbidity in patients with chronic heart failure (HF), endothelial injury in patients with coronary artery disease, and arrhythmias. This revision aims to discuss the role of sVCAM-1 as a biomarker to predict the occurrence, development, and preservation of cardiovascular disease.     

The blood concentration of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in patients with active thyroid-associated orbitopathy before and after methylprednisolone treatment

BACKGROUND: The soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) have been found to be increased in the blood of patients with Graves disease. The aim of this study is evaluation of the serum concentrations of soluble forms of adhesion molecules ICAM-1 and VCAM-1 in patients with thyroid-associated orbitopathy (TAO) before and after methylprednisolone treatment. MATERIAL AND METHODS: The study was performed in 40 Graves disease, hyperthyroid and euthyroid patients with a clinically active form of TAO. Serum concentrations of sVCAM-1 and sICAM-1 in TAO patients were determined by enzymelinked immunoabsorbent assay (ELISA) before and after intensive pulse methylprednisolone treatment. RESULTS: We did not find any significant changes in the studied parameters between TAO patients with hyperthyroidism and those with euthyroidism. The serum concentrations of sICAM-1 and sVCAM-1 were significantly increased in patients with TAO before methylprednisolone therapy when compared with the control group. After treatment serum concentrations of sICAM-1 and sVCAM-1 decreased significantly but were still significantly higher than for the control group. CONCLUSION: From the results obtained we can conclude that Graves orbitopathy itself but not thyroid function is probably responsible for the elevated level of the adhesion molecules studied.     

Insulin-like growth factor 1 opposes the effects of C-reactive protein on endothelial cell activation

Emerging evidence demonstrates that high plasma C-reactive protein (CRP) levels or low plasma insulin-like growth factor 1 (IGF-1) concentrations may be separately associated with the increased risk of coronary artery disease or myocardial infarction. Interestingly, animal model studies and epidemiological investigations indicate that circulating IGF-1 and CRP levels have an inverse correlation. The present study aims to evaluate if IGF-1 can directly oppose the effects of CRP on endothelial cell (EC) activation. We found that IGF-1 rescues endothelial nitric oxide synthase activity and decreases the release of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 from ECs. We also showed that IGF-1 antagonizes the effects of CRP by activating the PI3K/Akt pathway and suppressing the JNK/c-Jun and MAPK p38/ATF2 signaling pathways, rather than inhibiting ERK1/2 activity. These findings provide evidence of the physiopathological mechanisms of endothelial activation and novel insights into the protective properties of IGF-1.     

Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-D-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 +/- 2.0%) and high (17.4 +/- 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level (P = 0.012) and muscle (P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake (P = 0.040) and glucose extraction rate (P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 (P < 0.05) and lower coronary flow reserve (P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.     

Inhibition of cholesteryl ester transfer protein by anacetrapib does not impair the anti-inflammatory properties of high density lipoprotein

Cholesteryl ester transfer protein (CETP) is a target of therapeutic intervention for coronary heart disease. Anacetrapib, a potent inhibitor of CETP, has been shown to reduce LDL-cholesterol by 40% and increase HDL-cholesterol by 140% in patients, and is currently being evaluated in a phase III cardiovascular outcomes trial. HDL is known to possess anti-inflammatory properties, however with such large increases in HDL-cholesterol, it is unclear whether CETP inhibition perturbs HDL functionality such as anti-inflammatory effects on endothelial cells. The purpose of the present study was to determine whether CETP inhibition by anacetrapib affects the anti-inflammatory properties of HDL. HDL was isolated from either hamsters treated with vehicle or anacetrapib for 2 weeks, or from normal human subjects treated either placebo, 20 mg, or 150 mg anacetrapib daily for 2 weeks. Anacetrapib treatment increased plasma HDL cholesterol levels by 65% and between 48 and 82% in hamsters and humans, respectively. Pre-incubation of human aortic endothelial cells with HDL isolated from both control and anacetrapib treated hamsters suppressed TNFα induced expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Similar results were obtained with human HDL samples pre and post treatment with placebo or anacetrapib. Further, HDL inhibited TNFα-induced MCP-1 secretion, monocyte adhesion and NF-κB activation in endothelial cells, and the inhibition was similar between control and anacetrapib treated groups. These studies demonstrate that anacetrapib treatment does not impair the ability of HDL to suppress an inflammatory response in endothelial cells.     

Angiogenic factors in women ten years after severe very early onset preeclampsia

Background

Women with a history of mainly severe and early onset preeclampsia have an increased risk of future cardiovascular disease. During these complicated pregnancies increased levels of anti-angiogenic factors can be found. We hypothesize that women with a history of severe very early onset preeclampsia still have increased levels of these biomarkers years after this pregnancy, resulting in increased risk for cardiovascular disease.

Methods

Twenty women with severe early onset preeclampsia before 24 weeks'' gestation, who delivered between 1993–2003 in a tertiary referral centre and twenty matched controls with uncomplicated pregnancies and healthy term infants, were addressed for participation in the study. Venous plasma samples were analyzed for basic fibroblast growth factor (bFGF), placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), E- and P-selectin, soluble intercellular adhesion molecule-3 (sICAM-3) and thrombomodulin by ELISA.

Results

Sixteen case subjects and 18 control subjects consented participation. The median time interval index pregnancy to study was 9.4 and 9.7 years for cases and controls, respectively. Median levels for cases-controls (p-value) were not different; bFGF: 17.43–11.11 pg/mL (0.33), sFlt-1: 102.98–101.92 pg/ml (0.84), PLGF: 3.57–4.20 pg/mL (0.38), VEGF: 64.05–45.72 pg/mL (0.73), E-selectin: 5.11–4.68 ng/mL (0.20), P-selectin: 85.35–71.69 ng/mL (0.69), sICAM-3: 0.42–0.63 ng/mL (0.41) and Thrombomodulin: 0.92–0.93 ng/mL (0.59).

Conclusion

There were no differences in angiogenic biomarkers between women with a history of severe early onset preeclampsia versus uncomplicated pregnancy almost 10 years later, suggesting that these angiogenic factors will not contribute to the early detection of women at risk for future cardiovascular disease.     

A truncated recombinant intercellular adhesion molecule-1 inhibits adhesion of leukemic cell lines to upregulated endothelial cells

Summary Intercellular adhesion molecule-1, a member of the immunoglobulin supergene family, is the ligand for the integrin lymphocyte function associated antigen-1. Intercellular adhesion molecule-1 and lymphocyte function associated antigen-1 binding interactions mediate leukocyte adherence and migration. Previous work has shown that the adherence of lymphocyte function associated antigen-1 is directed to the first immunoglobulinlike domain of the endothelial cell surface protein intracellular adhesion molecule-1. We have constructed a truncated intercellular adhesion molecule-1 gene encoding the first 185 amino acids from the amino terminus and overexpressed it inEscherichia coli. The recombinant protein was purified from insoluble inclusion bodies and refolded into an active conformation by a denaturation/renaturation cycle. The identity of the protein was confirmed by microsequencing and by Western blot analysis using a polyclonal antibody to ICAM-1. We have demonstrated that this soluble region of the otherwise membrane-bound ligand is an inhibitor of Molt or HL-60 cell adhesion to cytokine-stimulated endothelial cells.     

Inhibition of macrophage adhesion activity by 9trans,11trans-conjugated linoleic acid

Conjugated linoleic acids (CLAs) have anti-atherogenic effects in both in vitro and animal models. Most studies on CLAs were performed with either a CLA mixture or purified 9cis (Z),11trans (E)-CLA or 10E,12Z-CLA isomers. However, the 9E,11E isomer has superior anti-carcinogenic and anti-inflammatory effects compared with the more abundant CLAs. The 9E,11E-CLA isomer specifically increases interleukin-1 receptor antagonist (IL-1Ra), an important anti-inflammatory mediator that is associated with decreased risk of coronary heart disease. The purpose of this present study was to determine if 9E,11E-CLA affects markers of atherogenesis via regulation of IL-1Ra. In human umbilical vein endothelial cells (HUVECs), 9E,11E-CLA decreased such atherogenesis-related genes as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, E-selectin, P-selectin and C–C motif chemokine receptor-2. Treatment of RAW 264.7 cells with 9E,11E-CLA decreased their adhesion to HUVECs. This effect was reversed by inhibiting the phosphoinositide 3-kinase or mouse target of rapamycin pathways. IL-1Ra-deficient RAW 264.7 cells (siIL-1Ra RAW) bind more efficiently to HUVECs compared with the control stable cells (si-control RAW). In addition, HUVECs treated with siIL-1Ra RAW-conditioned media induce significantly higher levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1 and E-selectin than HUVECs treated with si-control RAW-conditioned media. Taken together, the data show that 9E,11E-CLA decreases the atherogenesis-related genes in HUVECs and alters adhesion of macrophages. In addition, the induction of IL-1Ra by 9E,11E-CLA is partially responsible for the anti-atherogenic properties of this particular CLA isomer.     

Changes of cytokines during the course of graft-versus-host disease following bone marrow transplantation: a case report

Allogeneic bone marrow transplantation was performed in a 24-year-old woman with acute myelogenous leukemia in the first remission (FAB classification: M4). Graft-versus-host disease occurred from around day 150 after bone marrow transplantation. The levels of tumour necrosis factor-alpha, interleukin 12, and intercellular adhesion molecule-1 were elevated in the early stage of graft-versus-host disease, followed by elevation of interleukin 10 and interleukin 8. Her symptoms subsequently improved and all of these parameters became normal. The levels of thrombomodulin and plasminogen activator inhibitor type 1 showed changes that were in parallel with the clinical course. Interleukin 1beta, interleukin 6, interleukin 2, and interferon-gamma showed no changes throughout the course of her graft-versus-host disease. These findings suggested the possibility that release of inflammatory molecules occurred at the onset of graft-versus-host disease and caused vascular endothelial damage, which led to the exacerbation of her disease.     

Lipid peroxidation and inflammatory molecules as markers of coronary artery disease

Oxidized low density lipoproteins (oxLDLs) may exert several pro-inflammatory effects that can contribute to the development of coronary artery disease (CAD). Evaluating a possible correlation between oxLDLs and clinical expression of CAD, we measured specific lipid peroxidation indices in healthy subjects and in patients at different clinical stages of CAD. We observed a slight, but not significant, increase in plasma content of cholesterol oxidation products, i.e. oxysterols, in all CAD patients, and a slight, but not significant, increase of 4-hydroxynonenal-protein adducts only in subjects with acute CAD. Moreover, CAD patients showed a plasma rise of specific inflammatory proteins, i.e. C-reactive protein, intercellular adhesion molecule-1, and interleukin-8, but not of monocyte chemotactic protein-1. These preliminary data, without excluding an involvement of oxidative stress and inflammation in CAD, do not show a strict correlation between relevant plasma markers, other than C-reactive protein, and acute phase of the disease.     

HMG-CoA reductase inhibitors reduce adhesion of human monocytes to endothelial cells.

HMG-CoA reductase inhibitors (statins) are believed to reduce coronary heart disease by mechanisms in addition to their well-known cholesterol-lowering effect. We studied the effect of these drugs on monocyte cell adhesion to endothelium. Pretreatment of monocytic cells (U937, THP-1, human CD14(+) monocytes) with 0.01-10 microM concentrations of atorvastatin, cerivastatin, or simvastatin significantly reduced cell adhesion to endothelium. In contrast, pretreatment of endothelium with statins did not affect adhesion of monocytes. Adhesion of monocytes to vascular cell adhesion molecule-1-coated dishes was reduced by these drugs. Cerivastatin also reduced PMA induction of NF-kappaB. Since monocyte adhesion to endothelium is an early event in atherogenesis, treatment with statins in prevention of coronary heart disease may have additional salutary effects to lowering of plasma LDL cholesterol. Our results indicate that the reduction of monocyte adhesion by HMG-CoA reductase inhibitors may be considered as a class effect.     

Social networks and inflammatory markers in the Framingham Heart Study

Lack of social integration predicts coronary heart disease mortality in prospective studies; however, the biological pathways that may be responsible are poorly understood. The specific aims of this study were to examine whether social networks are associated with serum concentrations of the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Participants in the Framingham Study attending examinations from 1998 to 2001 (n=3267) were eligible for inclusion in the study. Social networks were assessed using the Berkman-Syme Social Network Index (SNI). Concentrations of IL-6, CRP, sICAM-1 and MCP-1 were measured in fasting serum samples. Multivariable linear regression analyses were used to assess the association of social networks with inflammatory markers adjusting for potential confounders including age, smoking, blood pressure, total:HDL cholesterol ratio, body mass index, lipid-lowering and antihypertensive medication, diabetes, cardiovascular disease, depression and socioeconomic status. Results found that the SNI was significantly inversely associated with IL-6 in men (p=0.03) after adjusting for potential confounders. In age-adjusted analyses, social networks also were significantly inversely associated with IL-6 for women (p=0.03) and were marginally to modestly associated with CRP and sICAM-1 for men (p=0.08 and 0.02, respectively), but these associations were not significant in the multivariate analyses. In conclusion, social networks were found to be inversely associated with interleukin-6 levels in men. The possibility that inflammatory markers may be potential mediators between social integration and coronary heart disease merits further investigation.     

The influence of garlic (Allium sativum) extract on interleukin 1alpha-induced expression of endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1.

Inflammation plays an important role in both the initiation of atherosclerosis and development of atherothrombotic events. The adherence of leukocytes/monocytes to the endothelium is an early event in atherogenesis. Phytotherapeutica as garlic and garlic extracts were shown to have beneficial modulating effects in patients with atherosclerotic disease. The aim of this study was to evaluate in vitro the influence of water-soluble garlic (Allium sativum) extract on the cytokine-induced expression of endothelial leukocyte adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1, CD54) and vascular cell adhesion molecule-1 (VCAM-1, CD106). Cytokine-induced expression of cellular adhesion molecules was measured on primary human coronary artery endothelial cell (HCAEC) cultures. HCAEC were cultured in microvascular endothelial cell growth medium and preincubated with garlic extract at various concentrations (0.25-4.0 mg/ml), after which human interleukin-1alpha (IL-1alpha, 10 ng/ml) was added for 1 day. Fluorescein isothiocyanate (FITC)-labeled anti-ICAM-1 and FITC-labeled anti-VCAM-1 were used to analyze the IL-1alpha-induced expression of ICAM-1 and VCAM-1 by flow cytometry. Incubation of HCAEC with garlic extract significantly decreased ICAM-1 and VCAM-1 expression induced by IL-1alpha. In addition, we examined the effects of garlic extract on the adhesion of monocytes to endothelial cells, using the monocytic U937 cell line. The presence of garlic extract significantly inhibited the adhesion of monocytes to IL-1alpha-stimulated endothelial cells. These results indicate that garlic extract modulates the expression of ICAM-1 and VCAM-1, thus potentially contributing to the beneficial effects traditionally attributed to garlic.     

Interleukin-6, but not soluble adhesion molecules, predicts a subsequent mortality from cardiovascular disease in patients with acute ST-segment elevation myocardial infarction

Inflammatory responses are an important element in the atherosclerotic process. Therefore, inflammatory markers can potentially serve as predictors of cardiovascular risk. However, the existing data are limited and controversial. We conducted a prospective cohort study with 263 patients with first acute ST-segment elevation myocardial infarction (STEMI) who were admitted to our Hospital within 6 h after the symptoms onset. Clinical data were recorded and serum admission levels of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble P-selectin (sP-selectin) were determined. The patients were then followed up for 3 years to document cardiovascular mortality. During the follow-up, 34 patients died from cardiovascular causes. The admission levels of IL-6 were significantly higher in these patients, whereas sICAM-1, sVCAM-1, and sP-selectin were comparable between these and the survived patients. The Kaplan–Meier plots revealed a significant increase in cardiovascular mortality with increasing levels of IL-6 (P = 0.0002, χ² test). The logistic regression analysis indicated that IL-6 was an independent predictor for cardiovascular mortality. To conclude, our findings indicate that elevated admission levels of IL-6, but not soluble adhesion molecules, provide valuable information for risk assessment of long-term cardiovascular mortality in patients with STEMI.     

Family with Sequence Similarity 5, Member C (FAM5C) Increases Leukocyte Adhesion Molecules in Vascular Endothelial Cells: Implication in Vascular Inflammation

Identification of the regulators of vascular inflammation is important if we are to understand the molecular mechanisms leading to atherosclerosis and consequent ischemic heart disease, including acute myocardial infarction. Gene polymorphisms in family with sequence similarity 5, member C (FAM5C) are associated with an increased risk of acute myocardial infarction, but little is known about the function of this gene product in blood vessels. Here, we report that the regulation of the expression and function of FAM5C in endothelial cells. We show here that FAM5C is expressed in endothelial cells in vitro and in vivo. Immunofluorescence microcopy showed localization of FAM5C in the Golgi in cultured human endothelial cells. Immunohistochemistry on serial sections of human coronary artery showed that FAM5C-positive endothelium expressed intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1 (VCAM-1). In cultured human endothelial cells, the overexpression of FAM5C increased the reactive oxygen species (ROS) production, nuclear factor-κB (NF-κB) activity and the expression of ICAM-1, VCAM-1 and E-selectin mRNAs, resulting in enhanced monocyte adhesion. FAM5C was upregulated in response to inflammatory stimuli, such as TNF-α, in an NF-κB- and JNK-dependent manner. Knockdown of FAM5C by small interfering RNA inhibited the increase in the TNF-α-induced production of ROS, NF-κB activity and expression of these leukocyte adhesion molecule mRNAs, resulting in reduced monocyte adhesion. These results suggest that in endothelial cells, when FAM5C is upregulated in response to inflammatory stimuli, it increases the expression of leukocyte adhesion molecules by increasing ROS production and NF-κB activity.