Early diagnosis of venous thromboembolism as a clinical primary symptom of occult cancer: Core proteins of a venous thrombus.

Malignancy is one of the risk factors of venous thromboembolism (VTE). As a common accompanying factor of malignant tumors, almost 20% of idiopathic VTEs are identified in patients with occult types of cancer as the primary symptom. The type of internal association that exists between malignant tumors and VTE has not yet been determined. The present review discusses the following: i) Reversible combinations between core proteins of venous thrombi and their ligand proteins. With the condition of immune cell balancing function collapse, which is characterized as dysfunction immune cells and impaired immune functions, the human body loses the function of eliminating infectious/malignant cells quickly and effectively. Thus, integrins ß2 and ß3 on the membrane of platelets and white blood cells are activated to combine with fibrinogen ligands to form an intravenous mesh-like structure, which acts as an intravenous biological filter that prevents infectious/malignant cells from flowing back into the circulatory system. During the defense process, blood cells (mainly red blood cells) stagnate and fill the filter, which results in venous thrombotic diseases. ii) Tumor cells, which cannot be eliminated quickly, proliferate and invade; or ischemic necrosis destroys peripheral tissues and vessels (veins and arteries), resulting in the formation of a biological filter in injured veins. The filter is filled with stranded tumor cells, which prevents the hemorrhagic metastasis of malignant cells. The formation of an intravenous biological filter results from the transition of the body's own defense capabilities, which is also a physical/histopathological phenomenon. iii) An increase in the number of core proteins in a venous thrombus is a basic molecular step in the formation of intravenous biological filters, which is also defined as a marker of the newly initiated defensive barrier. Increased levels of integrins ß1, ß2 and ß3 are useful in not only the specific diagnosis of VTE, but also in the early recognition of occult malignant tumors in idiopathic VTE patients.

Immune Cell Repertoire and Their Mediators in Patients with Acute Myocardial Infarction or Stable Angina Pectoris.

Background: To evaluate the natural innate and adaptive immunity through gene expression and cytology levels in peripheral blood mononuclear cells in patients with acute myocardial infarction (AMI), stable angina pectoris (SAP) and controls. Methods: 210 patients with AMI, 210 with SAP, and 250 clinical controls were recruited. Whole human genome microarray analysis was performed in 20 randomly chosen subjects per group were examined to detect the expressions of complement markers, natural killer cells, T cells and B cells. The quantity of these cells and related cytokines as well as immunoglobulin levels were measured in all subjects. Results: In AMI group, the mRNA expressions of late complement component, markers of natural killer cells, CD3+, CD8+ T cells and B cells were down-regulated, while those of early complement component and CD4+T cells were up-regulated (p<0.05). In both AMI and SAP patients, the quantity of natural killer cells, CD3+, CD8+ T cells, B cells, IgM and IgG were significantly lower than those of the controls. CD4+ T cells, CH50, C3, C4, IL-2, IL-4, IL-6 and IFN-γ were significantly higher (p<0.05). Conclusions: In AMI patients, both of gene expressions related to complement, natural killer cells, CD3+, CD8+ T cells, B cells and the quantity of these immune cells decreased while cell number reduced in SAP patients. Immune function in both AMI and SAP patients decreased especially in AMI patients with declined gene and protein levels. To improve the immune system is a potential target for medical interventions and prevention in AMI.

Depletion of complement system immunity in patients with myocardial infarction.

The aim of the present study was to evaluate differences in the expression of complement system genes, and serum levels of CH50, C3 and C4 in peripheral blood mononuclear cells from patients with myocardial infarction (AMI), stable angina pectoris (SA) and controls. A total of 100 patients with AMI, 100 with SA and 100 clinical controls were recruited in the present study. In each group, 20 randomly selected individuals were examined using whole human genome microarray analysis to detect the expression of genes of the complement system. The serum levels of CH50, C3 and C4 were measured in all 300 subjects. In the patients with AMI, the expression levels of genes encoding C1qα, C1qß, C1qγ, C1r, Factor P, C5a (complement component), CR1, integrin αM, integrin αX, integrin ß2, C5aR, CRIg (complement receptors) and CD46, CD55 and CD59 (complement regulators) were significantly higher, compared with the respective genes in the SA patients and controls (P<0.05), whereas the mRNA levels of C1s, C7, C8ß and C9 were the lowest in this group (P<0.05). No statistically significant differences were found in the gene expression levels of complement components or regulators between the SA and control groups. The serum levels of CH50, C3 and C4 were significantly increased in the AMI and SA groups, compared with the controls. In the AMI and SA groups, the complement system was activated. However, the differential mRNA expression of complement components, receptors and regulators in the AMI group suggested the dysfunction of the C5b-9 complex. The depression of complement system immunity in the patients with AMI may be associated with the pathogenesis of AMI.

Characteristics of B cell­associated gene expression in patients with coronary artery disease.

The current study aimed to identify differentially expressed B cell­associated genes in peripheral blood mononuclear cells and observe the changes in B cell activation at different stages of coronary artery disease. Groups of patients with acute myocardial infarction (AMI) and stable angina (SA), as well as healthy volunteers, were recruited into the study (n=20 per group). Whole human genome microarray analysis was performed to examine the expression of B cell­associated genes among these three groups. The mRNA expression levels of 60 genes associated with B cell activity and regulation were measured using reverse transcription­quantitative polymerase chain reaction. The mRNA expression of the B cell antigen receptor (BCR)­associated genes, CD45, NFAM, SYK and LYN, were significantly upregulated in patients with AMI; however, FCRL3, CD79B, CD19, CD81, FYN, BLK, CD22 and CD5 mRNA expression levels were significantly downregulated, compared with patients in the SA and control group. The mRNA levels of the T­independent B cell­associated genes, CD16, CD32, LILRA1 and TLR9, were significantly increased in AMI patients compared with SA and control patients. The mRNA expression of genes associated with T­dependent B cells were also measured: EMR2 and CD97 were statistically upregulated, whereas SLAMF1, LY9, CD28, CD43, CD72, ICOSL, PD1, CD40 and CD20 mRNAs were significantly downregulated in AMI group patients compared with the two other groups. Additionally the gene expression levels of B cell regulatory genes were measured. In patients with AMI, CR1, LILRB2, LILRB3 and VAV1 mRNA expression levels were statistically increased, whereas, CS1 and IL4I1 mRNAs were significantly reduced compared with the SA and control groups. There was no statistically significant difference in B cell­associated gene expression levels between patients with SA and the control group. The present study identified the downregulation of genes associated with BCRs, B2 cells and B cell regulators in patients with AMI, indicating a weakened T cell­B cell interaction and reduced B2 cell activation during AMI. Thus, improving B2 cell­mediated humoral immunity may be a potential target for medical intervention in patients with AMI.

Differential expression of T cell-related genes in AMI and SA stages of coronary artery disease.

OBJECTIVE: To identify differentially expressed T cells-related genes in peripheral blood mononuclear cells and compare their differences in T cell activation and subset functions in different stages of coronary atherosclerosis disease (CAD). METHODS: 20 patients with acute myocardial infarction patients (AMI), 20 patients with stable angina pectoris (SA) and 20 healthy volunteers were recruited into the study. Whole human genome microarray analysis was used to detect the expression of T cell related genes among three groups. RESULTS: mRNA expression of 68 genes involved in T cell was detected. 1) Antigen recognition: in the AMI patients 12 genes were down-regulated and 9 were significantly down-regulated among all 13 genes, compared with those of the SA and the control group, respectively. 2) Co-stimulators and regulators of T cell activation: among 16 genes in the AMI patients, 15 genes were lower and 8 were significantly lower than the other two groups. 3) T cell subsets, CTL: all 11 genes in the AMI patients were down-regulated, particularly GZMM and CASP8 were significantly down-regulated compared with the SA patients and controls. Th1/Th2: in the AMI patients, gene expressions including IL1 and IL18 were significantly higher, whereas GATA3 mRNA was significantly lower than those in other two groups. Th17/Treg: in the AMI group, RORC and CCR6 mRNAs were significantly down-regulated compared with the control group, while CD25 and CD127 expressions were significantly lower than SA group. There was no difference in T cell related genes between the SA patients and the controls. CONCLUSIONS: In the AMI patients, the mRNA expression of T cell antigen recognition, activation and subset functions was imbalanced or decreased, indicating the dysfunction of cellular immunity in patients with AMI. Then improving T cell mediated cellular immunity may be considered as a potential target for medical interventions in the patients with AMI.

Increased Expressions of Integrin Subunit ß1, ß2 and ß3 in Patients with Acute Infection.

OBJECTIVE: Our previous studies have shown that integrin subunits ß1, ß2 and ß3 were the core proteins of venous thrombi and potential useful biomarker of venous thromboembolism (VTE). Patients with acute infection have a high risk of VTE. In this study we explored that is there any relevance between core proteins and acute infection. METHODS: A total of 230 patients (112 females) with clinically proven acute infection in the emergency unit were recruited into this study, meanwhile 230 patients without acute infection matched in sex and age were recruited as control group. Flow cytometry was done to measure the expressions of blood integrin ß1, ß2, ß3 and cellular immunity (CD3, CD4, CD8, CD4/CD8, CD16CD56 and CD19). The association degree between increased core proteins and acute infection was analyzed by calculating the relative risk (RR). RESULTS: The expression of integrin ß1, ß2 and ß3 was markedly increased in patients with acute infection (P=0.000, 0.000 and 0.015, respectively). The relative risk ratio (RR) of increased integrin ß1, ß2 and ß3 in acute infection patients was 1.424 (95%CI: 1.156-1.755, P=0.001), 1.535 (95%CI: 1.263-1.865, P=0.000) and 1.20 (95%CI: 0.947-1.521, P=0.148), respectively. Combined integrin ß1, ß2 and ß3 analysis showed that the relative risk ratio (RR) of increased in patients with acute infection was 2.962 (95%CI: 1.621-5.410, P=0.001), and this relative risk (RR) rise to 3.176 (95%CI: 1.730-5.829, P=0.000) in patients with respiratory tract infection (RTI). CONCLUSION: As the core proteins of venous thrombi, integrinß1, ß2 and ß3 were markedly increased expression in patients with acute infection, which maybe explain the increased risk of VTE in acute infection patients. A weakened immune system could be the basic condition of VTE occurrence.

Characterization of immune cells and perforin mutations in familiar venous thromboembolism.

AIM: This study was to carry out exome sequencing in a Han Chinese family with venous thromboembolism. METHODS: Three venous thromboembolism (VTE) patients and five members from a Han Chinese family were evaluated by exome sequencing. RESULTS: Among the 3 VTE patients, mutations of 2 genes including PRF1 and HTR2A were identified and predicted to be functionally damaged to their encoded proteins. In addition, the PRF1 mutation and the HTR2A mutation identified in our study were absent in 100 non-related controls, indicating that venous thromboembolism has a genetic component. The R357W mutation is located in the membrane attack complex/perforin domain of PRF1 protein, which exists in both the perforin. The steps of killing foreign or pathological antigen cells by NK cells, CD8 (+)T cells and the membrane attack complex include membrane perforation and release of the granzyme, either of which is abnormal can lead to immune dysfunction. CONCLUSIONS: The mutations of immune related genes in familial VTE might provide new understanding of the pathogenesis of familial venous thromboembolism.

Expression characteristics of neutrophil and mononuclear-phagocyte related genes mRNA in the stable angina pectoris and acute myocardial infarction stages of coronary artery disease.

OBJECTIVE: To investigate expression differences of neutrophil and mononuclear phagocyte related gene mRNAs among acute myocardial infarction (AMI), stable angina (SA) and control groups, and then discuss their expression characteristics in the stable angina pectoris (SAP) and AMI stages of coronary artery disease (CAD). METHODS: Whole Human Genome Oligo Microarrays were applied to assess the differential expression characteristics of neutrophil and mononuclear phagocyte related mRNAs in patients with AMI (n = 20), SA (n = 20) and controls (n = 20). RESULTS: (1) Almost all colony-stimulating factors (CSF) and their receptors related mRNAs was up-regulated in AMI and SA groups compared with the control group, and the expression of granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) and granulocyte colony stimulating factor receptor (G-CSFR) mRNAs in the AMI group was significantly up-regulated compared with the other two groups (P < 0.01). (2) The expression of mRNAs related to monocyte chemoattractant protein-1 (MCP-1), CCR2 (MCP-1 receptor) and CXCR2 (IL-8 receptor) was significantly up-regulated (P < 0.01) in AMI group compared with SA and control groups. IL-8 mRNA expression in the AMI group was clearly higher than the controls (P < 0.05). (3) All mRNAs expression related to opsonic receptors (IgG FcR and C3bR/C4bR) was significantly up-regulated in AMI group compared with SA and control group (P < 0.01), and the SA group showed an upward trend compared with controls. (4) Most pattern recognition receptor (PRR)-related mRNAs expression was up-regulated in AMI group compared with SA and control groups. Most toll-like receptor (TLR) mRNAs expression was significantly up-regulated (P < 0.01) than the SA and control groups; macrophage scavenger receptor (MSR) mRNA was significantly up-regulated in AMI group compared with the control group (P < 0.01), and the SA group showed an upward trend compared with the controls. CONCLUSIONS: The expression of most neutrophil and mononuclear-macrophage function related genes mRNAs was significantly up-regulated by stages during the progression of CAD, suggesting that the adhesive, chemotactic and phagocytic functions of neutrophil and mononuclear-macrophage were strengthened in the occurrence and development of coronary atherosclerosis and AMI. This also showed a stepped upward trend as the disease progressed.

Significantly reduced function of T cells in patients with acute arterial thrombosis.

OBJECTIVES: To explore the intrinsic factors related to the pathogenesis of acute arterial thrombosis (AAT) and to elucidate the pathogenesis of AAT on the basis of differentially expressed genes. METHODS: Patients with acute myocardial infarction (AMI), stable angina (SA) and healthy controls (n = 20 per group) were recruited, and the whole human genome microarray analysis was performed to detect the differentially expressed genes among these subjects. RESULTS: Patients with AMI had disease-specific gene expression pattern. Biological functional analysis showed the function of T cells was significantly reduced, the mitochondrial metabolism significantly decreased, the ion metabolism was abnormal, the cell apoptosis and inflammatory reaction increased, the phagocytosis elevated, the neutrophil-mediated immunity increased and the post-traumatic repair of cells and tissues increased in AMI patients. The biological function in SA group and healthy controls remained stable and was comparable. CONCLUSIONS: The reduced function of T cell gene models in AAT showed the dysfunction of the immune system. The pathogenesis of AAT may be related to the inflammatory reaction after arterial intima infection caused by potential pathogenic microorganisms.

Internal relationship between symptomatic venous thromboembolism and risk factors: up-regulation of integrin ß1, ß2 and ß3 levels.

BACKGROUND: To compare different expression of core proteins among venous thromboembolism (VTE) and those with risk factor groups and analyze the relative risk for VTE after integrating integrin ß1, ß2 and ß3 expression. METHODS: A total of 1006 subjects were recruited and divided into VTE group, risk factor groups and control (non- risk factor) group. Flow cytometry was performed to detect the expression of integrin ß1, ß2 and ß3. The relative risk for VTE was evaluated with independent, parallel and serial methods. RESULTS: The expression of integrin ß1 increased markedly in VTE patients, and those with risk factors (acute infection, malignancy, and autoimmune diseases), respectively (P < 0.001 or 0.01). The expression of integrin ß1 in trauma/surgery group was not significantly different with control group (P > 0.05). The expression of integrin ß2 or ß3 significantly increased in VTE group, but that in risk factor groups was not significantly increased (P > 0.05). Multivariate analysis revealed the trauma/surgery groups had no significantly increased risk for VTE. CONCLUSIONS: VTE group patients have significantly increased expression of integrin ß1, ß2 and ß3, and risk factor groups (acute infection, malignancy and autoimmune disease) have significantly increased expression of integrin ß1. The significant increase in integrin ß2, ß3 expression is a marker differentiating of VTE group patients with other risk factor groups. Trauma/surgery group has no increased expression of integrin ß1, ß2 and ß3 as other risk factors. Thus, that trauma/surgery may be not the "true" risk factor for VTE.

Increased expressions of integrin subunit ß1, ß2 and ß3 in patients with cancer ------correlation analysis between risk factors of VTE and expression of core proteins.

OBJECTIVE: Cancer is one of the most common risk factor of venous thromboembolism (VTE). Our previous studies have shown that integrin subunits ß1, ß2 and ß3 were the core proteins of venous thrombi and potential useful biomarker of VTE. This study aimed to explore the expression status of core proteins (integrin subunits ß1, ß2 and ß3) in cancer patients. METHODS: This is a case-control study. A total of 144 inpatients (54 females) with clinically proven cancers were recruited into this study, meanwhile 200 inpatients without cancer matched in sex and age were recruited as control group. Flow cytometry was done to measure the expressions of blood integrin ß1, ß2, ß3 and cellular immunity related variables (CD3, CD4, CD8, CD4/CD8, CD16CD56 and CD19). The association degree between increased core proteins and cancers was analyzed by calculating the relative risk (RR). RESULTS: The expression of integrin ß1 and ß3 were markedly increased in patients with cancer (P=0.001 and 0.008). Integrin ß2 was also mildly increased in patients with cancer (P=0.274). The relative risk ratio (RR) of increased integrin ß1, ß2 and ß3 in cancer patients was 1.655 (95% CI: 1.321-2.074, P=0.000), 1.314 (95% CI: 1.052-1.642, P=0.021) and 1.852, (95% CI: 1.097-3.126, P=0.028), respectively. Combined analysis with integrin ß1, ß2 and ß3 showed that the relative risk ratio (RR) of increased in cancer patients was 4.895 (95% CI: 1.645-14.563, P=0.002). CD3, CD4, CD4/CD8 and CD19 were significantly decreased (P=0.004, P=0.000, P=0.000, P=0.000, respectively) in patients with cancer, while CD8 and CD16CD56 were markedly increased in cancer patients (P=0.005, P=0.035). CONCLUSIONS: As the core proteins of venous thrombi, integrin ß1 and ß3 were markedly increased expression in patients with cancer, which maybe explain the increased risk of VTE in cancer patients. A weakened or disordered immune system might be the basis of VTE in condition.

Differential expression of 5-HT-related genes in symptomatic pulmonary embolism patients.

OBJECTIVE: Whole human genome oligo microarrays were employed to systematically investigate the mRNA expression profile of 5-HT synthetase, transporter, receptor, and factors in 5-HT signaling pathway in peripheral blood karyocytes from pulmonary embolism (PE) patients. METHODS: A total of 20 PE patients and 20 healthy subjects matched in gender and age were recruited. The human genome microarrays were performed to detect the mRNA expression profile of 5-HT synthetase, transporter, receptor, and factors in 5-HT signal pathway of two groups. The random variance model corrected t-test was used for analysis. RESULTS: Our results showed (1) tryptophan hydroxylase (TPH1)-related gene expression was markedly down-regulated in PE patients (P < 0.01); (2) monoamine oxidases (MAO)-related gene (MAOB) expression was significantly up-regulated in PE patients (P < 0.01); (3) the expression of 17 genes of 7 5-HT receptors showed a down-regulated tendency in PE patients, and significant difference was observed in the expression of HTR1E, HTR3B, HTR4 and HTR5A between them (P < 0.05); (4) the expression of DalDAG-GEF I, Tubby, PKA and EPAC in 5-HT signal pathways was dramatically up-regulated in PE patients (P < 0.05); the expression of SPA1, RIAM, RAPL, Talin, PKC, PLC and Pyk2 was remarkably up-regulated in PE patients (P < 0.05); (5) the expression of integrin genes ITGA2B, ITGB1 and ITGB3 was significantly up-regulated in PE patients (P < 0.05). CONCLUSION: In PE patients, the expression of TPH1 and HTR4 was down-regulated as a negative feedback; the MAOB expression was up-regulated. Consistent with the expression of 5-HTR1E and 5-HTR4 and the abnormally activated Tubby, the expression of integrins in platelets was activated.

The origin and onset of acute venous thrombus.

Under the condition of immune cell balancing function collapse, acute venous thrombosis originates from intravenous immune adhesive inflammations triggered by cells which are infected by foreign pathogenic microorganism and malignant cells. With the condition of immune cell balancing function collapse, the human body lost the function of clearing intravenous foreign pathogenic microorganism and malignant cells timely and effectively. Thus, integrins ß2 and ß3 on the membrane of white blood cells and platelets are activated to combine with the ligand fibrinogen into a reversible mesh-like structure, which is like the intravenous biological filter and acts as physical defense of the human body to prevent the cells which are infected by foreign pathogenic microorganism and malignant cells in the distal veins from flowing back to the whole body. Meanwhile, blood cells mainly red blood cells stagnate and fulfill the filter, which blocks the blood flow in the local veins and thus results in venous thrombotic diseases. People with collapsed immune cell balancing functions are the certain groups of people who will develop venous thromboembolism. Anyone who had venous thromboembolism indicates alloantigen cells in the veins, which are mainly pathogenic microorganism infected cells and malignant cells and trigger the onset of venous thromboembolism. Only under the condition of immune cell balancing function collapse, the risk factors, such as advanced age, infection, trauma, surgery, autoimmune disease, pregnancy as well as long trip syndrome, could cause venous thromboembolism.

Analysis of the protein-protein interaction networks of differentially expressed genes in pulmonary embolism.

The aim of the present study was to explore the function and interaction of differentially expressed genes (DEGs) in pulmonary embolism (PE). The gene expression profile GSE13535, was downloaded from the Gene Expression Omnibus database. The DEGs 2 and 18 h post­PE initiation were identified using the affy package in R software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the DEGs were analyzed using Database for Annotation Visualization and Integrated Discovery (DAVID) online analytical tools. In addition, protein­protein interaction (PPI) networks of the DEGs were constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins. The PPI network at 18 h was modularized using Clusterone, and a functional enrichment analysis of the DEGs in the top three modules was performed with DAVID. Overall, 80 and 346 DEGs were identified 2 and 18 h after PE initiation, respectively. The KEGG pathways, including chemokine signaling and toll­like receptor signaling, were shown to be significantly enriched. The five highest degree nodes in the PPI networks at 2 or 18 h were screened. The module analysis of the PPI network at 18 h revealed 11 hub nodes. A Gene Ontology terms analysis demonstrated that the DEGs in the top three modules were associated with the inflammatory, defense and immune responses. The results of the present study suggest that the DEGs identified, including chemokine­related genes TFPI2 and TNF, may be potential target genes for the treatment of PE. The chemokine signaling pathway, inflammatory response and immune response were explored, and it may be suggested that these pathways have important roles in PE.

Expression of B-cell-associated genes in peripheral blood mononuclear cells of patients with symptomatic pulmonary embolism.

The aim of the present study was to identify differentially expressed B­cell­associated genes in peripheral blood mononuclear cells and investigate the gene expression characteristics of the different stages of B­cell activation. A total of 20 patients with pulmonary embolisms (PE) and 20 age­ and gender­matched controls were enrolled in the present study. Human complementary DNA microarray analysis was used in order to detect the differential expression of B­cell­associated genes between the PE and control groups. Messenger (m)RNA expression was detected for 82 genes involved in B­cell activation. The results showed that PE patients exhibited significantly increased expression levels of the B­cell receptor genes LYN, CD22, SYK, BTK, PTPRC and NFAM1, whereas expression levels of FYN, FCRL4 and LAX1 were significantly decreased compared to those of the control group. Expression levels of T­cell­dependent B­cell­activation genes, including EMR2, TNFSF9, CD86, ICOSLG, CD37 and CD97, were significantly upregulated in PE patients, whereas SPN mRNA expression was significantly downregulated compared with those of the control group. LILRA1 and TLR9 T cell­independent B­cell activation mRNAs were significantly upregulated in PE patients compared with those of the control group. In addition, the expression levels of B­cell­activation regulator genes, including CR1, LILRB4 and VAV1, were significantly increased, whereas SLAMF7 expression levels were significantly decreased in PE patients compared with those of the control group. Furthermore, the expression levels of B­cell­activation­associated cytokine genes demonstrated a significant upregulation of LTA and IL10 and downregulation of L1A, IFNA5, IFNA6, IFNA8, IFNA14, IL2, IL13 and IFNG in PE patients compared to those of the control group. In conclusion, the differential gene expression at different stages of B­cell activation between healthy controls and PE patients indicated that B­cell function was reduced or disorganized in patients with symptomatic PE.

Comparison of cytokine expressions in acute myocardial infarction and stable angina stages of coronary artery disease.

OBJECTIVE: To investigate the differential gene expression of cytokines and compare their impacts on the immune functions among the acute myocardial infarction patients (AMI), the stable angina patients (SA) and the controls. METHODS: 20 patients with AMI, 20 patients with SA and 20 healthy volunteers were recruited into the study. Whole human genome microarray analysis was used to detect the gene expression differences in interferons, interleukins, chemokines, tumor necrosis factors and associated receptors in peripheral blood mononuclear cells (PBMCs) among three groups. RESULTS: Compared with SA patients and the controls respectively, in AMI patients, IFNα2, IFNαR1, IFNαR2, IFNγR1, IFNγR2, L1ß, IL16, IL18, Cxcl1, Cxcl2, Cxcl6, CxcR2, CxcR4, LIGHT, TNFR1, LT-ßR, CD137, TRAILR, and TWEAKR mRNA expressions were significantly up-regulated (P<0.05), while Ccl5, Ccl24, Ccl28, CcR5, TWEAK, CD40, CD27, and BAFFR mRNA expressions were significantly down-regulated (P<0.05). But, there was no significant difference in cytokine expression between the SA patients and the controls. CONCLUSION: In AMI patients, mRNA expression levels of cytokines were imbalanced, indicating the dysfunction of the immune system. Together with no significant change of cytokines was observed between the SA and controls, showing the different cytokine related immune activity in the AMI and SA patients.

Differential loss of natural killer cell activity in patients with acute myocardial infarction and stable angina pectoris.

BACKGROUND: To evaluate the activity of natural killer cells through their inhibitory and activating receptors and quantity in peripheral blood mononuclear cells extracted from patients with acute myocardial infarction, stable angina pectoris and the controls. METHODS: 100 patients with myocardial infarction, 100 with stable angina, and 20 healthy volunteers were recruited into the study. 20 randomly chosen people per group were examined for the whole human genome microarray analysis to detect the gene expressions of all 40 inhibitory and activating natural killer cell receptors. Flow cytometry analysis was applied to all 200 patients to measure the quantity of natural killer cells. RESULTS: In myocardial infarction group, the mRNA expressions of six inhibitory receptors KIR2DL2, KIR3DL3, CD94, NKG2A, KLRB1, KLRG1, and eight activating receptors KIR2DS3, KIR2DS5, NKp30, NTB-A, CRACC, CD2, CD7 and CD96 were significantly down-regulated (P<0.05) compared with both angina patients and the controls. There was no statistical difference in receptor expressions between angina patients and control group. The quantity of natural killer cells was significantly decreased in both infarction and angina patients compared with normal range (P<0.001). CONCLUSIONS: The significant mRNAs down-regulation of several receptors in myocardial infarction group and reduction in the quantity of natural killer cells in both myocardial infarction and angina patients showed a quantitative loss and dysfunction of natural killer cells in myocardial infarction patients.

Increased expressions of integrin subunit ß1, ß2 and ß3 in patients with venous thromboembolism: new markers for venous thromboembolism.

OBJECTIVE: To investigate the core proteins (integrin subunits ß1, ß2 and ß3) in the acute venous thrombi and validate the specificity and sensitivity of increased expression of integrin subunits ß1, ß2 and ß3 in patients with venous thromboembolism. METHODS: A total of 120 patients (73 females) with clinically proven acute VTE and aged between 24-90 years, and 120 non-VTE patients and healthy controls receiving physical examination matched in the sex and age were recruited. Flow cytometry was done to measure the expressions of blood integrin ß1, ß2 and ß3. The receiver-operator characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of integrin ß1, ß2 and ß3. RESULTS: The median levels of integrin ß1, ß2 and ß3 were significantly higher in VTE patients than in non-VTE patients (P=0.000, 0.000 and 0.000, respectively) and healthy controls (P=0.000, 0.000 and 0.000, respectively). The ROC curves showed that integrin ß1, ß2 and ß3 were specific diagnostic predictors of VTE with an area under the curve (AUC) of 0.870, 0.821, and 0.731, respectively. When three integrins were combined for diagnosis, the AUC of ROC curve was 0.916, and the sensitivity, specificity, positive and negative predictive values were 84.6%, 90.8%, 81.7% and 92.0%, respectively. CONCLUSION: The increased integrin ß1, ß2 and ß3, as the core protein of venous thrombosis, have relatively high specificity and sensitivity for VTE and thus may serve as useful new biomarkers for the diagnoses of VTE.

Relationship of high CH50 level and interruption of cascade reaction of complement mRNA expression in acute venous thromboembolism patients.

In patients with pulmonary embolism (PE), forepart components of complements were activated. However there are interruption/decrease of cascade reaction and cytolytic effects in complement system. This study detected CRP, CH50, C3 and C4 levels in patients with venous thromboembolism (VTE) and compare with the imbalance of complement associated gene mRNA expression in PE patients. There was significant increase of CH50 in acute VTE patients. Even though CH50 increased significantly in acute VTE patients and had a relatively high sensitivity, cytolytic effects of complements might decrease, based on the genomics results of complement cascade reactions imbalance/interruption and increased total complements in VTE patients.

Venous thromboembolism is a product in proliferation of cancer cells.

The pathogenesis of venous thromboembolism (VTE) in patients with cancer is related to the destruction of small veins and the intravenous formation of filamentous mesh-like structure by fibrinogen. The filamentous mesh-like filter can block hematogenous metastasis of cancer cells and also can stagnate blood cells, leading to venous thrombosis. Cancer cells have characteristics of malignancy and fast proliferation, and ischemic necrosis frequently occurs, and small veins were invaded and damaged. The formation of filamentous mesh-like structure has defense function and also may cause the occurrence of VTE. VTE is a product of the proliferation process of malignant cells.