Atherosclerosis is an inflammatory disease as well as a lipid disorder. Atherosclerotic plaque formed in vessel walls may cause ischemia, and the rupture of vulnerable plaque may result in fatal events, like myocardial infarction or stroke. Because morphological imaging has limitations in diagnosing vulnerable plaque, molecular imaging has been developed, in particular, the use of nuclear imaging probes. Molecular imaging targets various aspects of vulnerable plaque, such as inflammatory cell accumulation, endothelial activation, proteolysis, neoangiogenesis, hypoxia, apoptosis, and calcification. Many preclinical and clinical studies have been conducted with various imaging probes and some of them have exhibited promising results. Despite some limitations in imaging technology, molecular imaging is expected to be used both in the research and clinical fields as imaging instruments become more advanced.
Atherosclerosis/*diagnosis/pathology/radiography ; Endothelial Cells/metabolism ; Humans ; Inflammation/pathology ; Lipoproteins, LDL/metabolism ; Macrophages/immunology/metabolism ; Plaque, Atherosclerotic ; Positron-Emission Tomography ; Tomography, Emission-Computed, Single-Photon

The effect of thymic stromal lymphopoietin (TSLP) on macrophage-derived foam cell formation and the underlying mechanism were studied. Macrophages isolated from C57BL/6 mice were co-cultured in vitro with different concentrations of TSLP or TSLPR-antibody in the presence of oxidized low density lipoprotein (ox-LDL). The effects of TSLP on macrophage-derived foam cell formation were observed by using oil red O staining and intracellular lipid determination. The expression levels of foam cell scavenger receptors (CD36 and SRA) as well as ABCA1 and TSLPR were detected by using RT-PCR and Western blotting. As compared with the control group, TSLP treatment significantly promoted lipid accumulation in macrophages, significantly increased protein expression of CD36 and TSLPR in a dose-dependent manner, and significantly reduced the expression of ABCA1 protein in a dose-dependent manner. No significant differences were noted between the TSLPR-antibody group and the control group. TSLP may down-regulate the expression of cholesterol efflux receptor ABCA1 and up-regulate scavenger receptor expression via the TSLPR signaling pathway, thereby promoting macrophage-derived foam cell formation.
ATP Binding Cassette Transporter 1 ; genetics ; metabolism ; Animals ; Antibodies ; immunology ; pharmacology ; Blotting, Western ; CD36 Antigens ; genetics ; metabolism ; Cells, Cultured ; Cholesterol ; metabolism ; Cholesterol Esters ; metabolism ; Cytokines ; pharmacology ; Dose-Response Relationship, Drug ; Foam Cells ; cytology ; drug effects ; metabolism ; Gene Expression ; drug effects ; Immunoglobulins ; immunology ; metabolism ; Lipoproteins, LDL ; pharmacology ; Macrophages ; cytology ; drug effects ; metabolism ; Mice ; Mice, Inbred C57BL ; Receptors, Cytokine ; immunology ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Scavenger Receptors, Class A ; genetics ; metabolism

OBJECTIVETo observe the effect of andrographolide on the activation of mitogen-activated protein kinases (MAPKs) and expression of nuclear factor-κB (NF-κB) in macrophage foam cells.

METHODSThe mouse peritoneal macrophages were cultured in the media in the presence of oxidized low-density lipoprotein (ox-LDL), ox-LDL+andrographolide, or neither (control). The phosphorylation of MAPK molecules (p38MAPK, JNK, ERK1/2) and the expressions of NK-κB p65 were examined by Western blot.

RESULTSAs compared with cells in the control group, the expressions of phospho-p38 and NF-κB p65 were increased in the cells cultured with either ox-LDL or ox-LDL+andrographolide (P<0.01), but attenuated significantly in the presence of ox-LDL+ andrographolide when compared with ox-LDL (P<0.05). The phospho-JNK increased in the presence of either ox-LDL or ox-LDL+andrographolide when compared with control cells (P<0.01), but no significant difference existed between ox-LDL and ox-LDL+andrographolide (P>0.05). The expression of phospho-ERK1/2 was increased in the presence of ox-LDL compared with the control cells (P<0.01), but no significant differences existed between the cells cultured in the presence of ox-LDL+andrographolide and the control medium (P>0.05).

CONCLUSIONSAndrographolide could inhibit the activation of ERK1/2, p38MAPK and NK-κB induced by ox-LDL in macrophage foam cells, which might be one of its mechanisms in preventing atherosclerosis.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Atherosclerosis ; immunology ; metabolism ; prevention & control ; Cells, Cultured ; Diterpenes ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Foam Cells ; cytology ; drug effects ; enzymology ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Lipoproteins, LDL ; metabolism ; MAP Kinase Signaling System ; drug effects ; immunology ; Macrophages, Peritoneal ; cytology ; drug effects ; enzymology ; Mice ; Mice, Inbred Strains ; NF-kappa B ; metabolism ; Vasculitis ; drug therapy ; immunology ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo examine the effect of ginsenoside Rb1 (GRb1) on the immune maturation of monocyte-derived dendritic cells (DCs) induced by oxidized low-density lipoprotein (OX-LDL).

METHODSHuman monocytes purified by CD14+ immuno-magnetic beads were differentiated and induced into immature DCs, which were randomly divided into 6 groups, Group A treated with PBS, Group B treated with OX-LDL, Group C and D treated respectively with GRb1 and ciglitazone, Group E and F were pretreated with the two testing drugs respectively followed by OX-LDL. The immuno-phenotypic expression (CD40, CD1a, and HLA-DR) and endocytosis function of DCs were examined using flow cytometry, the concentration of interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-alpha) in the culture supernatants were measured with ELISA.

RESULTSCompared with Group B, Group E showed significantly lowered immuno-phenotypic expression of DCs in terms of CD40 (67.4 +/- 1.62 vs. 145.69 +/- 14.86), CD1a (79.64 +/- 3.04 vs. 159.89 +/- 6.09), and HLA-DR (46.43 +/- 2.85 vs. 99.33 +/- 17.11), as well as higher endocytosis level (88.13% +/- 1.06% vs. 25.90% +/- 5.77%, all P < 0.01). Meantime, the serum levels of IL-12 (88.65 +/- 5.59 ng/L vs. 716.69 +/- 36.35 ng/L) and TNF-alpha (133.27 +/- 11.98 ng/L vs. 968.10 +/- 36.42 ng/L) obviously decreased (P < 0.01). The surface molecular expression of DCs and the secretion of inflammatory factors in Group F also obviously decreased, showing insignificant difference from Group E (P > 0.05).

CONCLUSIONGRb1 could obviously inhibit the OX-LDL-induced maturation of DCs, showing similar effects to ciglitazone.

Cell Differentiation ; drug effects ; Cells, Cultured ; Dendritic Cells ; cytology ; drug effects ; immunology ; Flow Cytometry ; Ginsenosides ; pharmacology ; Humans ; Lipoproteins, LDL ; Monocytes ; cytology ; drug effects ; immunology

PURPOSE: Low grade inflammation is a well-known characteristic in obese subjects. We investigated body weight changes and inflammatory markers after 12-week intervention trial. MATERIALS AND METHODS: Twenty-six obese subjects were enrolled and 19 (13 men and 6 women) completed the study. Sibutramine is an FDA-approved drug for body weight control; therefore, we chose this drug as the standard treatment medication in this study. Patients were randomly allocated to receive an anti-inflammatory agent (Diacerein treatment group; n = 12) or placebo (n = 7) for 12 weeks. Anthropometry, body proportion by dual-energy X-ray absorptiometry, and metabolic parameters at the beginning and end of study were measured and compared. RESULTS: The treatment group had a tendency towards more reduction in anthropometry as compared to the placebo group, in body weight reduction (- 7.0 kg vs. - 4.6 kg), body mass index (- 2.51 kg/m2 vs. - 1.59 kg/m2), and waist circumference (- 7.3 cm vs. - 4.4 cm). These reductions were not statistically significant. Changes in levels of high-sensitivity C-reactive protein and adiponectin in the treatment group were more favorable than in the placebo group. CONCLUSION: This small pilot study showed no statistical difference for changes in anthropometry, and inflammatory markers between the two groups. Therefore, we could not find any additional effects of Diacerein on weight loss and inflammatory variables in this study.
Absorptiometry, Photon ; Adiponectin/blood ; Adult ; Anthraquinones/*therapeutic use ; Anti-Inflammatory Agents/*therapeutic use ; Appetite Depressants/therapeutic use ; C-Reactive Protein/analysis ; Cyclobutanes/*therapeutic use ; Double-Blind Method ; Female ; Humans ; Inflammation ; Lipoproteins, LDL/blood ; Male ; Obesity/*drug therapy/immunology ; Pilot Projects ; Tumor Necrosis Factor-alpha/blood ; Waist Circumference/drug effects/immunology ; Weight Loss/drug effects/*immunology

It has been hypothesized that blood infusion of reconstituted HDL (rHDL) is a possible therapeutic strategy for the treatment of coronary artery disese. To compare short-term anti-inflammatory activity of wildtype (WT) apoA-I and point mutants, each rHDL containing WT, V156K, or R173C was infused into apo-E deficient atherosclerotic mice. Each rHDL was injected via the tail vein at a dosage of 120 mg/kg of body weight in 0.4 ml of tris-buffered saline (TBS), and blood was then collected at 24 and 48 h post-injection. Although regression activity was observed in each of the rHDL infused groups, a 30% reduction in the lipid-stained area of the aortic sinus was observed in the V156K and R173C-rHDL groups when compared to that of the WT-rHDL group, and this reduction was well correlated with an approximately 60% reduction in the accumulation of macrophages in the lesion area. Additionally, the groups that received the V156K and R173C-rHDL treatments showed smaller increases in the GOT, GPT, interleukin-6, myeloperoxidase (MPO) and lipid hydroperoxide (LPO) serum levels than those that received the WT-rHDL treatment. In addition, the strongest serum paraoxonase and ferric reducing ability was observed in the V156K and R173C-rHDL groups. In vitro nitration and chlorination of apoA-I by MPO treatment revealed that V156K-rHDL and R173C-rHDL were less susceptible to chlorination. Furthermore, rHDL treatment inhibited cellular uptake of oxidized LDL by macrophage cells and the production of proatherogenic species in culture media. In conclusion, blood infusions of the rHDLs exerted in vivo regression activity with anti-inflammatory and antioxidant activity in apo-E deficient mice and THP-1 cells, especially in those that were treated with V156K and R173C apoA-I.
Animals ; Anti-Inflammatory Agents/immunology/*therapeutic use ; Apolipoprotein A-I/blood/genetics/immunology/*therapeutic use ; Apolipoproteins E/genetics ; Aryldialkylphosphatase/blood/metabolism ; Atherosclerosis/*drug therapy ; Cell Line ; Cell Membrane Permeability ; Cholesterol/blood/metabolism ; Humans ; Lipoproteins, HDL/genetics/immunology/*therapeutic use ; Lipoproteins, LDL/metabolism ; Macrophages/cytology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxidation-Reduction/*drug effects ; Peroxidase/blood/metabolism ; Point Mutation

Atherosclerosis ; etiology ; prevention & control ; Cytokines ; secretion ; Dendritic Cells ; drug effects ; immunology ; Endocytosis ; Fenofibrate ; pharmacology ; Humans ; Immunophenotyping ; Lipoproteins, LDL ; toxicity ; Monocytes ; cytology ; PPAR alpha ; agonists ; physiology

UNLABELLEDTo investigate the effect of immune response mediated by the T cells stimulated with the specific antigen (oxidized low-density lipoprotein, oxLDL) on plaque stability in coronary heart disease.

METHODSThis study involved 20 patients with acute myocardial infarction (AMI), 34 with unstable angina pectoris (UAP), 27 with stable angina pectoris (SAP) and 22 healthy control subjects. With MTS/PMS colorimetric assay, the T cells from all the subjects were tested for proliferative response to stimulation by 5 microg/ml oxLDL and 5 microg/ml low-density lipoprotein (LDL). Interferon-gamma (IFN-gamma) concentration in the proliferative response of the T cells was measured with enzyme-linked immunosorbent assay (ELISA).

RESULTSThe proliferative response of the T cells elicited by 5 microg/ml oxLDL stimulation was significantly higher in the AMI and UAP groups than in the SAP and control groups (P<0.05). Similarly, IFN-gamma concentration in the proliferative response of the T cells to 5 microg/ml oxLDL stimulation was significantly higher in the former two groups (P<0.05). In the AMI and UAP groups, 5 microgLDL stimulation (P<0.001).

CONCLUSIONThe immune response mediated by the T cells to specific antigen stimulation, especially the immune response mediated by T helper type 1 (Th1) cells secreting IFN-gamma, may play an important role in the plaque instability and the occurrence of acute coronary syndrome.

Aged ; Coronary Disease ; immunology ; Female ; Humans ; Interferon-gamma ; secretion ; Lipoproteins, LDL ; immunology ; Male ; Middle Aged ; T-Lymphocytes ; immunology ; metabolism ; T-Lymphocytes, Helper-Inducer ; immunology ; metabolism

OBJECTIVETo investigate the relation of the levels of C-reactive protein (CRP) and antibodies against oxidized low-density lipoprotein (anti-oxLDL) to with acute coronary syndrome (ACS).

METHODSThe levels of CRP, anti-oxLDL and anti-LDL were measured and compared in 96 subjects including 26 with acute myocardial infarction (AMI), 29 with unstable angina pectoris (UAP), 20 with stable angina pectoris (SAP) and 21 control subjects to evaluate the relationship between CRP and anti-oxLDL.

RESULTSBoth CRP and anti-oxLDL levels in patients with ACS, including AMI and UAP, were significantly higher than those in SAP patients and the control subjects (P<0.05), but the level of anti-LDL showed no significant difference between the groups (P>0.05). There was significant positive correlation between the levels of CRP and anti-oxLDL (P<0.001).

CONCLUSIONThe specific immune response to oxLDL may play an important role in the instability of plaque and the occurrence of ACS, and anti-oxLDL level may serve as an important specific marker for the instability of plaque.

Aged ; Antibodies ; blood ; immunology ; Biomarkers ; blood ; metabolism ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Coronary Disease ; blood ; complications ; metabolism ; pathology ; Female ; Humans ; Lipoproteins, LDL ; immunology ; Male ; Middle Aged

OBJECTIVE: To detect the levels of index related to inflammation such as soluble CD40 ligand (sCD40L), neutrophil collagenase-8 (MMP-8), and pregnancy associated plasma protein-A (PAPP-A) , lipid peroxidation and autoimmune indexes such as oxidized low density lipoprotein (ox-LDL) and its antibody (ox-LDL Ab) in patients with coronary heart disease, and to investigate its relationship with acute coronary syndrome (ACS). METHODS: Contents of sCD40L, MMP-8, PAPP-A, ox-LDL and ox-LDL Ab in the peripheral blood were measured by enzyme-linked immunosorbent assay from 109 patients with coronary heart disease including 36 acute myocardial infarction (AMI), 38 unstable angina pectoris (UAP), and 35 stable angina pectoris (SAP) and 36 controls without coronary heart disease. RESULTS: The levels of each index in the peripheral blood of ACS patients (including AMI and UAP) were higher than those of SAP patients and controls (P < 0.05), and the difference of each index between UAP group and AMI group in ACS patients had no statistical significance (P > 0.05). The levels of each index of SAP patients, except PAPP-A, were all higher than those of controls (P <0.05). All the indexes were helpful in diagnosis of ACS. The area under the ROC curve of each index is between 0.7 and 0.9. CONCLUSION The increase of sCD40L, MMP-8, PAPP-A, ox-LDL and ox-LDL Ab levels in peripheral blood may be related to the pathogenesis of ACS, and can be used as potential markers of unstable atherosclerosis plaque.
Aged ; Angina, Unstable ; blood ; immunology ; Autoantibodies ; blood ; Biomarkers ; blood ; CD40 Ligand ; blood ; Coronary Artery Disease ; blood ; immunology ; Female ; Humans ; Lipoproteins, LDL ; blood ; immunology ; Male ; Matrix Metalloproteinase 8 ; blood ; Middle Aged ; Myocardial Infarction ; blood ; immunology ; Pregnancy-Associated Plasma Protein-A ; metabolism