ABSTRACT
BACKGROUND: There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions. OBJECTIVE: This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets. METHODS: This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test. RESULTS: Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function. CONCLUSION: CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.
Subject(s)
Aging , Frailty , Humans , Male , Female , Aged , Frailty/blood , Frailty/immunology , Cross-Sectional Studies , Aging/physiology , Aging/immunology , Aging/blood , Adult , CD28 Antigens/blood , Platelet Endothelial Cell Adhesion Molecule-1/blood , Cellular Senescence , T-Lymphocyte Subsets/immunology , Young Adult , Aged, 80 and over , Frail Elderly , Biomarkers/blood , Cognitive Dysfunction/blood , Cognitive Dysfunction/immunology , T-Lymphocytes/immunologyABSTRACT
ABSTRACT: A number of studies have demonstrated that exosomes were involved in important physiological and pathological processes through cell-to-cell communication in cardiovascular disease, which contained nucleic acids, proteins, and lipid contents. In our study, we found that the protein platelet endothelial cell adhesion molecule-1 (PECAM1) was an extracellular vesicle in the blood of high blood pressure patients (HBPP).Isolated the vesicles from the blood of HBPP and health examiners and detected its size and morphology with nanoparticle tracking analysis, then we identified its surface protein CD63, CD81, and the protein expression of PECAM1 in the exosome with western blot. Furthermore, we analyzed the correlation between the expression of PECAM1 and the high blood degree with linear regression analysis.Our results showed that the morphology of extracellular vesicles was more evident in high blood pressure groups than healthy controls, and the protein expression of PECAM1 was also abundant in the vesicles of HBPP, however, there were no extracellular vesicles in the blood samples of healthy controls. Besides, linear regression showed the linear correlation coefficient Râ=â0.901, Pâ<â.01 between the expression of PECAM1 and the systolic blood pressure of the high blood patients. Therefore, the exosome of protein of PECAM1 was a potential risking star in HBPP.
Subject(s)
Exosomes/genetics , Hypertension/genetics , Platelet Endothelial Cell Adhesion Molecule-1/blood , Adult , Blotting, Western , Extracellular Vesicles/genetics , Female , Heart Disease Risk Factors , Humans , Hypertension/blood , Linear Models , Male , Middle Aged , Nanoparticles/metabolism , Tetraspanin 28/metabolism , Tetraspanin 30/metabolismABSTRACT
Purpose To investigate the application value of serum CXC Chemokine-13 (CXCL-13) and platelet endothelial cell adhesion molecule-1 (PECAM-1) in elderly patients with gastric cancer (GC). Methods Ninety-eight elderly GC patients admitted to the Affiliated Hexian Memorial Hospital of Southern Medical University were selected as a research group, and 60 healthy subjects of the same age and in relatively good health who underwent physical examination at the same period were selected as a control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of CXCL13 and PECAM-1 in serum. The clinical diagnosis and prognostic value of serum CXCL13 and PECAM-1 in elderly GC patients were analyzed. Results The levels of CXCL13 and PECAM-1 in serum of the research group were significantly higher than those of the control group (P < 0.001). The AUC value of combined diagnosis of elderly GC patients by serum CXCL13 and PECAM-1 was 0.950, and that of combined evaluation of prognosis of patients was 0.849. Serum CXCL13 and PECAM-1 were significantly related to TNM staging, differentiation degree and tumor diameter in elderly GC patients (P < 0.05). High levels of CXCL13 and PECAM-1 were significantly associated with lower 5-year OS (P < 0.05). Conclusion Elderly GC patients with higher TNM staging, longer tumor diameters, high levels of CXCL13 and PECAM-1 had an increased risk of poor prognosis. Serum CXCL13 and PECAM-1 can be used as effective indicators for diagnosis and prognosis of elderly patients with GC, and can predict the 5-year OS in patients (AU)
Subject(s)
Humans , Aged , Chemokine CXCL13/blood , Platelet Endothelial Cell Adhesion Molecule-1/blood , Stomach Neoplasms/blood , Stomach Neoplasms/diagnosis , Biomarkers, Tumor/blood , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Kaplan-Meier Estimate , Prognosis , Stomach Neoplasms/mortalityABSTRACT
PURPOSE: To investigate the application value of serum CXC Chemokine-13 (CXCL-13) and platelet endothelial cell adhesion molecule-1 (PECAM-1) in elderly patients with gastric cancer (GC). METHODS: Ninety-eight elderly GC patients admitted to the Affiliated Hexian Memorial Hospital of Southern Medical University were selected as a research group, and 60 healthy subjects of the same age and in relatively good health who underwent physical examination at the same period were selected as a control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of CXCL13 and PECAM-1 in serum. The clinical diagnosis and prognostic value of serum CXCL13 and PECAM-1 in elderly GC patients were analyzed. RESULTS: The levels of CXCL13 and PECAM-1 in serum of the research group were significantly higher than those of the control group (P < 0.001). The AUC value of combined diagnosis of elderly GC patients by serum CXCL13 and PECAM-1 was 0.950, and that of combined evaluation of prognosis of patients was 0.849. Serum CXCL13 and PECAM-1 were significantly related to TNM staging, differentiation degree and tumor diameter in elderly GC patients (P < 0.05). High levels of CXCL13 and PECAM-1 were significantly associated with lower 5-year OS (P < 0.05). CONCLUSION: Elderly GC patients with higher TNM staging, longer tumor diameters, high levels of CXCL13 and PECAM-1 had an increased risk of poor prognosis. Serum CXCL13 and PECAM-1 can be used as effective indicators for diagnosis and prognosis of elderly patients with GC, and can predict the 5-year OS in patients.
Subject(s)
Chemokine CXCL13/blood , Platelet Endothelial Cell Adhesion Molecule-1/blood , Stomach Neoplasms/blood , Aged , Biomarkers, Tumor/blood , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Kaplan-Meier Estimate , Male , Prognosis , Stomach Neoplasms/diagnosis , Stomach Neoplasms/mortality , Survival RateABSTRACT
The current standard biomarker for myocardial infarction (MI) is high-sensitive troponin. Although powerful in clinical setting, search for new markers is warranted as early diagnosis of MI is associated with improved outcomes. Extracellular vesicles (EVs) attracted considerable interest as new blood biomarkers. A training cohort used for diagnostic modelling included 30 patients with STEMI, 38 with stable angina (SA) and 30 matched-controls. Extracellular vesicle concentration was assessed by nanoparticle tracking analysis. Extracellular vesicle surface-epitopes were measured by flow cytometry. Diagnostic models were developed using machine learning algorithms and validated on an independent cohort of 80 patients. Serum EV concentration from STEMI patients was increased as compared to controls and SA. EV levels of CD62P, CD42a, CD41b, CD31 and CD40 increased in STEMI, and to a lesser extent in SA patients. An aggregate marker including EV concentration and CD62P/CD42a levels achieved non-inferiority to troponin, discriminating STEMI from controls (AUC = 0.969). A random forest model based on EV biomarkers discriminated the two groups with 100% accuracy. EV markers and RF model confirmed high diagnostic performance at validation. In conclusion, patients with acute MI or SA exhibit characteristic EV biomarker profiles. EV biomarkers hold great potential as early markers for the management of patients with MI.
Subject(s)
Angina, Stable/blood , Biomarkers/blood , Epitopes/blood , Extracellular Vesicles/genetics , ST Elevation Myocardial Infarction/blood , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/metabolism , Acute Coronary Syndrome/pathology , Aged , Angina, Stable/genetics , Angina, Stable/pathology , CD40 Antigens/blood , Cohort Studies , Epitope Mapping , Epitopes/genetics , Female , Humans , Integrin alpha2/blood , Male , Middle Aged , P-Selectin/blood , Percutaneous Coronary Intervention , Platelet Endothelial Cell Adhesion Molecule-1/blood , Platelet Glycoprotein GPIb-IX Complex/genetics , ST Elevation Myocardial Infarction/genetics , ST Elevation Myocardial Infarction/pathologySubject(s)
Disease Management , Platelet Endothelial Cell Adhesion Molecule-1/blood , Pulmonary Arterial Hypertension/therapy , Pulmonary Circulation/physiology , Biomarkers/blood , Female , Humans , Male , Middle Aged , Prognosis , Pulmonary Arterial Hypertension/blood , Pulmonary Arterial Hypertension/physiopathologyABSTRACT
Disseminated intravascular coagulation (DIC) is a frequent complication of sepsis that affects patient outcomes due to accompanying thrombo-inflammation and microvascular permeability changes. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a cellular adhesion and signaling receptor that is expressed on both hematopoietic and endothelial cells, plays an important anti-inflammatory role in acute and chronic inflammatory disease models. Little is known, however, about role and mechanism of PECAM-1 in septic DIC. Here, we investigated whether PECAM-1 might play a protective role in hindering the development of septic DIC. Plasma levels of soluble PECAM-1 were markedly elevated in septic patients that developed DIC, with a correspondingly poorer outcome. PECAM-1 knockout exhibited more severe DIC and poorer outcome in the LPS induced- and cecal ligation and puncture-induced DIC model, which could be alleviated by tissue factor inhibitor. This phenomenon seemed to be equally linked to PECAM-1 expression by both endothelial and blood cells. Furthermore, PECAM-1 was found to exert its protective effect on developing septic DIC by the following 2 distinct mechanisms: the inhibition of macrophage pyroptosis and the acceleration of the restoration of the endothelial cell barrier. Taken together, these results implicate PECAM-1 as a potentially attractive target for the development of novel therapeutics to manage and treat septic DIC.
Subject(s)
Blood Vessels/pathology , Disseminated Intravascular Coagulation/prevention & control , Inflammation/pathology , Macrophages/pathology , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Pyroptosis , Animals , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/complications , Endothelial Cells/metabolism , Endothelial Cells/pathology , Female , Fibrinolysis , Humans , Lipopolysaccharides , Male , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Phenotype , Platelet Endothelial Cell Adhesion Molecule-1/blood , Platelet Endothelial Cell Adhesion Molecule-1/deficiency , Sepsis/blood , Sepsis/complications , Treatment OutcomeABSTRACT
D-Dimer has a high sensitivity but a low specificity for the diagnosis of deep vein thrombosis (DVT) which limits its implementation as a general screening parameter. There is a demand for additional biomarkers to improve its diagnostic accuracy. Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) is generated at the site of venous thrombosis, thus, represents a promising biomarker. Patients with clinically suspected DVT (N = 159) were prospectively recruited and underwent manual compression ultrasonography (CCUS) to confirm or exclude DVT. The diagnostic value of D-Dimer, sPECAM-1 and the combination of both was assessed. sPECAM-1 levels were significantly higher in patients with DVT (N = 44) compared to patients without DVT (N = 115) (85.9 [76.1/98.0] ng/mL versus 68.0 [50.1/86.0] ng/mL; p < 0.001) with a diagnostic sensitivity of 100% and a specificity of 28.7% at the cut point > 50.2 ng/mL. sPECAM-1 improved the diagnostic accuracy of D-Dimer: the combination of both biomarkers yielded a ROC-AUC of 0.925 compared to 0.905 for D-Dimer alone and 0.721 for sPECAM-1 alone with a reduction of false-positive D-Dimer cases 72- > 43 (Δ = - 31.9%). The discrimination mainly occurred in a subgroup of patients characterized by an inflammatory background (defined by c-reactive protein level > 1 mg/mL). sPECAM-1 represents a novel diagnostic biomarker for venous thrombosis. It does not qualify as a diagnostic biomarker alone but improves the diagnostic accuracy of D-Dimer in patients with suspected DVT.
Subject(s)
Fibrin Fibrinogen Degradation Products/analysis , Platelet Endothelial Cell Adhesion Molecule-1/blood , Venous Thrombosis/diagnosis , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Reproducibility of Results , Venous Thrombosis/bloodABSTRACT
BACKGROUND: Circulating endothelial cells (CEC) may be used to find new strategies for the early di-agnosis of cardiovascular diseases. The major objective of the project is to broaden knowledge of CEC biology by determining their phenotypic characteristics. The additional aim is to clarify whether on the basis of these information it is possible to identify the origin of CEC release (from various cardiovascular compartments). METHODS: Circulating endothelial cells were collected from arterial blood prior to angiography, as well as from arterial and venous blood obtained after angiography/coronary angioplasty, from 18 patients with non-ST-segment elevation myocardial infarction (NSTEMI). CECs were quantified by flow cytometry and defined as Syto16 (dye)+, CD45dim/neg, CD31+ and CD146+. The additional CD36+ was establish as a marker of endothelial cells released from small vessels of the microcirculation. RESULTS: The total number of CECs increased significantly after the percutaneous transluminal coronary angioplasty (PTCA) in the arterial system. Number of CECs isolated at similar time points (after invasive procedure) did not differ significantly between arteries and veins, but the number of CD36+ CECs after coronary angioplasty was significantly higher in the venous system, than in the arterial system. CONCLUSIONS: The number of CD36+ in artery samples obtained after coronary angioplasty (PTCA) had tendency to be decreased (in comparison to the sample obtained before angiography). It was major difference between those who had PTCA performed vs. those who had not.
Subject(s)
CD36 Antigens/blood , Echocardiography , Endothelial Cells/metabolism , Non-ST Elevated Myocardial Infarction/blood , Ventricular Dysfunction, Left/blood , Ventricular Function, Left , Aged , Biomarkers/blood , CD146 Antigen/blood , Coronary Angiography , Endothelial Cells/pathology , Female , Flow Cytometry , Humans , Leukocyte Common Antigens/blood , Male , Middle Aged , Non-ST Elevated Myocardial Infarction/diagnostic imaging , Non-ST Elevated Myocardial Infarction/physiopathology , Non-ST Elevated Myocardial Infarction/therapy , Percutaneous Coronary Intervention , Phenotype , Platelet Endothelial Cell Adhesion Molecule-1/blood , Predictive Value of Tests , Treatment Outcome , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/therapyABSTRACT
BACKGROUND: Delirium is the most common postoperative complication of the central nervous system (CNS) that can trigger long-term cognitive impairment. Its underlying mechanism is not fully understood, but the dysfunction of the blood-brain barrier (BBB) has been implicated. The serum levels of the axonal damage biomarker, phosphorylated neurofilament heavy subunit (pNF-H) increase in moderate to severe delirium patients, indicating that postoperative delirium can induce irreversible CNS damage. Here, we investigated the relationship among postoperative delirium, CNS damage and BBB dysfunction, using pNF-H as reference. METHODS: Blood samples were collected from 117 patients within 3 postoperative days. These patients were clinically diagnosed with postoperative delirium using the Confusion Assessment Method for the Intensive Care Unit. We measured intercellular adhesion molecule-1, platelet and endothelial cell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin as biomarkers for BBB disruption, pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6), and pNF-H. We conducted logistic regression analysis including all participants to identify independent biomarkers contributing to serum pNF-H detection. Next, by multiple regression analysis with a stepwise method we sought to determine which biomarkers influence serum pNF-H levels, in pNF-H positive patients. RESULTS: Of the 117 subjects, 41 were clinically diagnosed with postoperative delirium, and 30 were positive for serum pNF-H. Sensitivity and specificity of serum pNF-H detection in the patients with postoperative delirium were 56% and 90%, respectively. P-selectin was the only independent variable to associate with pNF-H detection (P < 0.0001) in all 117 patients. In pNF-H positive patients, only PECAM-1 was associated with serum pNF-H levels (P = 0.02). CONCLUSIONS: Serum pNF-H could be an objective delirium biomarker, superior to conventional tools in clinical settings. In reference to pNF-H, P-selectin may be involved in the development of delirium-related CNS damage and PECAM-1 may contribute to the progression of delirium- related CNS damage.
Subject(s)
Biomarkers/blood , Central Nervous System/physiopathology , Delirium/blood , Neurofilament Proteins/blood , Postoperative Complications/blood , Aged , Axons/metabolism , Axons/pathology , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/physiopathology , Central Nervous System/metabolism , Central Nervous System/surgery , Delirium/etiology , Delirium/physiopathology , Disease Progression , E-Selectin/blood , Female , Humans , Intercellular Adhesion Molecule-1/blood , Male , Middle Aged , P-Selectin/blood , Platelet Endothelial Cell Adhesion Molecule-1/blood , Postoperative Complications/pathology , Vascular Cell Adhesion Molecule-1/bloodABSTRACT
BACKGROUND: Hypobaric hypoxia has been reported to cause endothelial cell and platelet dysfunction implicated in the formation of microvascular lesions, and in its extremes may contribute to vascular leakage in high altitude pulmonary edema or blood brain barrier disruption leading to cerebral micro-hemorrhage (MH). Platelet function in the development of microvascular lesions remained ill defined, and is still incompletely understood. In this study platelet- and endothelial cell-derived extracellular vesicles (PEV and EEV, respectively) and cell adhesion molecules were characterized in plasma samples of members of a high altitude expedition to delineate the contribution of platelets and endothelial cells to hypobaric hypoxia-induced vascular dysfunction. METHODS AND FINDINGS: In this observational study, platelet and endothelial cell-derived extracellular vesicles were analysed by flow-cytometry in plasma samples from 39 mountaineers participating in a medical research climbing expedition to Himlung Himal, Nepal, 7,050m asl. Megakaryocyte/platelet-derived AnnexinVpos, PECAM-1 (CD31) and glycoprotein-1b (GP1b, CD42b) positive extracellular vesicles (PEV) constituted the predominant fraction of EV in plasma samples up to 6,050m asl. Exposure to an altitude of 7,050m led to a marked decline of CD31pos CD42neg EEV as well as of CD31pos CD42bpos PEV at the same time giving rise to a quantitatively prevailing CD31neg CD42blow/neg subpopulation of AnnexinVpos EV. An almost hundredfold increase in the numbers of this previously unrecognized population of CD31neg CD42blow/neg EV was observed in all participants reaching 7,050m asl. CONCLUSIONS: The emergence of CD31neg CD42blow/neg EV was observed in all participants and thus represents an early hypoxic marker at extreme altitude. Since CD31 and CD42b are required for platelet-endothelial cell interactions, these hypobaric hypoxia-dependent quantitative and phenotypic changes of AnnexinVpos EV subpopulations may serve as early and sensitive indicators of compromised vascular homeostasis.
Subject(s)
Altitude , Annexin A5/blood , Endothelial Cells/pathology , Extracellular Vesicles/pathology , Hypoxia/physiopathology , Platelet Endothelial Cell Adhesion Molecule-1/blood , Acclimatization , Endothelial Cells/metabolism , Extracellular Vesicles/metabolism , Humans , Middle AgedABSTRACT
Aim: to evaluate the associations between signatures of apoptotic endothelial cell-derived microvesicles (MVs) with phenotypes of chronic heart failure (HF). Methods: The study cohort consisted of 388 prospectively involved subjects with HF patients with predominantly reduced left ventricular ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF) and HF with mid-range ejection fraction (HFmrEF). All biomarkers were measured at baseline. Results: The number of circulating CD31+/annexin V+ MVs in HFrEF and HFmrEF patients was similar. The number of circulating CD144+/annexin V+ MVs in HFrEF patients was significantly higher than HFmrEF and HFpEF. We determined that a combination of number of circulating CD31+/annexin V+ MVs and Gal-3 was the best predictor of HFpEF and that number of circulating CD144+/annexin V+ MVs is able to increase predictive capabilities of soluble ST2 (sST2) and Gal-3 for HFrEF. Conclusion: We found that the number of circulating CD31+/annexin V+ MVs may improve a predictive capacity for conventional HF biomarkers.
Subject(s)
Cell-Derived Microparticles/metabolism , Cell-Derived Microparticles/pathology , Endothelial Cells/pathology , Heart Failure/blood , Annexin A5/blood , Antigens, CD/blood , Biomarkers/blood , Blood Proteins , Cadherins/blood , Cohort Studies , Extracellular Vesicles/pathology , Female , Galectin 3/blood , Galectins , Heart Failure/physiopathology , Humans , Interleukin-1 Receptor-Like 1 Protein/blood , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Phenotype , Platelet Endothelial Cell Adhesion Molecule-1/blood , Prospective Studies , Stroke Volume , Ventricular RemodelingABSTRACT
The CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has been widely proved effective on relapsed and refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL). Meanwhile, CAR-T therapy-related toxicities, including cytokine release syndrome (CRS) and neurological toxicities, are drawing researchers' attention. In addition, our research team notices that coagulopathy and even disseminated intravascular coagulation (DIC) are common problems during CAR-T therapy. In our phase 1/2 clinical trial (NCT02965092), 53 r/r B-ALL patients underwent leukapheresis on day - 11 and received lymphodepleting chemotherapy on day - 7 to day - 5. Finally, they received split infusions of anti-CD19 CAR-T cells on day 0 to day 2. Plasma concentrations of tissue factor (TF) and platelet endothelial cell adhesion molecular-1 (PECAM-1) were also measured to identify the mechanism of coagulation disorders. The overall 1-month remission rate of the 53 patients was 88.7%. During the treatment course, 19 patients experienced grade 3-4 CRS, 8 patients developed grade 2-3 neurological toxicities. Beyond that, 30 patients (30/53, 56.6%) suffered from coagulation disorders, and half of them should be diagnosed as DIC. Benefiting from replacement and anticoagulant therapy, 14 patients successfully got out of the conditions of DIC. Remarkably, the severity of coagulopathy was positively correlated with CRS grade. What is more, plasma TF and PECAM-1 levels indicated that vascular endothelial factors played key roles in the process of CRS-related coagulopathy. To conclude, coagulation disorders frequently happen during CAR-T therapy. TF and PECAM-1 are of great importance in the etiology and pathogenesis of coagulation problems. Early and proper interventions targeted at CRS-related coagulopathy contribute a lot to the control of side effects in CAR-T therapy.
Subject(s)
Disseminated Intravascular Coagulation , Immunotherapy, Adoptive , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Safety , Adolescent , Adult , Aged , Child , Child, Preschool , Disease-Free Survival , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/therapy , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Neoplasm Proteins/blood , Platelet Endothelial Cell Adhesion Molecule-1/blood , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Survival Rate , Thromboplastin/metabolism , Vascular Endothelial Growth Factor A/bloodABSTRACT
Rheumatoid arthritis (RA) is a chronic inflammatory and systemic disease characterized by endothelial activation. The main objective of this study was to verify the profile of cell adhesion molecules (CAM) in RA patients, and the influence of metabolic syndrome (MetS) and drugs used in the treatment of RA in this profile. A second objective was to propose models of prediction of activity in RA using these biomarkers. A total of 115 healthy individuals and 144 RA patients were enrolled. Disease activity was determined by DAS28 (disease activity score 28) based on erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein (DAS28-CRP). Serum CAM and plasminogen activator inhibitor type-1 (PAI-1), anthropometric and immunological parameters were measured. Vascular cell adhesion molecule-1 (VCAM-1) was significantly decreased, and PAI-1 was significantly higher in RA patients as compared to controls. Binary logistic regression analysis showed that VCAM-1, CRP, and tumor necrosis factor-α (TNF-α) predicted RA with a sensitivity of 95.9% and a specificity of 89.5%. 42.9% of the variance in DAS28-ESR and 49.2% of the variance in DAS28-CRP are explained by increased PAI-1, TNF-α, body mass index (BMI) and decreased platelet endothelial cell adhesion molecule 1 (PECAM-1). Our data show that lower levels of VCAM-1 are associated with RA independently of MetS, while increased PAI-1 levels were associated with both RA and MetS and increased selectins (E-selectin and P-selectin) were exclusively associated with MetS and not with RA. A model to predict disease activity based on PECAM-1, PAI-1, TNF-α, age and BMI is proposed.
Subject(s)
Arthritis, Rheumatoid/diagnosis , Cell Adhesion Molecules/blood , Metabolic Syndrome/metabolism , Plasminogen Activator Inhibitor 1/metabolism , Adult , Aged , Arthritis, Rheumatoid/metabolism , Biomarkers/metabolism , Blood Sedimentation , Body Mass Index , C-Reactive Protein/metabolism , Case-Control Studies , Comorbidity , Female , Humans , Logistic Models , Male , Middle Aged , Platelet Endothelial Cell Adhesion Molecule-1/blood , Sensitivity and Specificity , Tumor Necrosis Factor-alpha/metabolism , Vascular Cell Adhesion Molecule-1/bloodABSTRACT
The aims of this study were to verify whether hyperhomocysteinemia is associated with disability progression in Multiple Sclerosis (MS) patients and whether TNF pathways and cellular adhesion molecules (CAM) are involved in this process. This study included 180 MS patients, who were divided according to their levels of homocysteine (Hyperhomocysteinemia ≥11.35 µmol/L) and 204 healthy individuals (control group). MS patients showed higher levels of homocysteine (p < 0.001), tumor necrosis factor alpha (TNF-α, p < 0.001), TNF receptor 1 (TNFR1, p = 0.038), TNF receptor 2 (TNFR2, p < 0.001), and lower levels of PECAM (p = 0.001), ICAM (p < 0.001) and VCAM (p = 0.005) than controls. The multivariate binary logistic regression analysis showed that plasma levels of homocysteine, TNFR1, TNFR2 and PECAM were associated with the presence of disease. MS patients with hyperhomocysteinemia showed higher disease progression evaluated by the Multiple Sclerosis Severity Score (MSSS, p < 0.001), disability evaluated by Expanded Disability Status Score EDSS (p < 0.001), TNFR1 (p = 0.039) and ICAM (p = 0.034) than MS patients with lower levels of homocysteine. Hyperhomocysteinemia was independently associated with MSSS in MS patients, but were not associated with TNF-α, TNFR, and CAM. Homocysteine levels was higher in progressive forms than relapsing-remitting MS (p < 0.001), independently of sex and age. In conclusion, this is the first study in which homocysteinemia was associated with progression of the disease (MSSS), although this finding was not directly related to TNF-α and TNFR pathways or to CAM.
Subject(s)
Homocysteine/blood , Hyperhomocysteinemia/complications , Multiple Sclerosis/blood , Adult , Disability Evaluation , Disease Progression , Female , Humans , Hyperhomocysteinemia/blood , Male , Middle Aged , Multiple Sclerosis/complications , Multiple Sclerosis/diagnosis , Platelet Endothelial Cell Adhesion Molecule-1/blood , Receptors, Tumor Necrosis Factor, Type I/blood , Receptors, Tumor Necrosis Factor, Type II/blood , Severity of Illness Index , Tumor Necrosis Factor-alpha/bloodABSTRACT
INTRODUCTION: Neovascularisation is a critical step in the progression of malignant tumors. Circulating endothelial progenitor cells (cEPC) have been proposed as surrogate markers of vasculogenesis in malignancies. In this project, we studied the impact of tumor-specific therapy on cEPC and associated angiogenic factors in patients with soft tissue tumors. MATERIALS AND METHODS: Fifty-three patients with soft tissue tumors (25 soft tissue sarcomas, 19 GIST, 9 desmoids) and 15 healthy controls were included. Blood samples were obtained at two time points, before and 8 weeks after start of tumor-specific therapy. Peripheral blood mononuclear cells (PBMCs) were isolated. cEPCs were characterised as CD34+, CD133+, CD45dim, CD31+ and vascular endothelial growth factor 2 (VEGFR-2) positive cells. Serum concentrations of VEGF-A and angiopoetin-2 were determined by enzyme-linked immunosorbent assay. RESULTS: VEGF-A and Ang-2 concentrations were significantly higher in tumor patients than in healthy controls in both samples (p < .01). Sarcoma patients with progressive disease developed a significant increase in cEPC levels between the two blood samples compared to those with stable disease (p = .002). GIST patients with progressive tumor or metastatic disease showed significant increase in VEGF-A values (p = .01). DISCUSSION: The pre-treatment values of the angiogenic markers did not correlate with the clinical course of the disease. However, cEPCs levels were significantly higher in sarcoma patients with progressive disease compared to those with stable disease and should be further evaluated as early markers of disease progression in sarcoma patients. VEGF-A and angiopoetin-2 clearly play a role as mediators of the vasculogenesis contributing to tumor progression.
Subject(s)
Biomarkers, Tumor/blood , Endothelial Progenitor Cells/pathology , Neovascularization, Pathologic/blood , Neovascularization, Pathologic/pathology , Soft Tissue Neoplasms/blood , Soft Tissue Neoplasms/pathology , AC133 Antigen/blood , Adult , Aged , Aged, 80 and over , Angiopoietin-2/blood , Antigens, CD34/blood , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Leukocyte Common Antigens/blood , Male , Middle Aged , Platelet Endothelial Cell Adhesion Molecule-1/blood , Prognosis , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor Receptor-2/bloodABSTRACT
CONTEXT: Non-invasive markers for diagnosis of acute rejection (AR) following liver transplantation have not been developed, yet. OBJECTIVE: We analyzed the correlation of plasma microparticle levels (MP) with AR. MATERIALS AND METHODS: MP (CD4, CD8, CD25, CD31, MHC) of 11 AR patients and 11 controls were analyzed within the first week after transplantation. RESULTS: CD4, CD8 and CD31 positive MP were higher in the AR, whereas overall MP count, CD25 and MHCI positive MP proportions did not differ between both groups. DISCUSSION AND CONCLUSION: MP dynamics within the first period of transplantation could help to clarify on-going mechanisms of immunomodulation.
Subject(s)
Cell-Derived Microparticles/metabolism , Graft Rejection/blood , Graft Rejection/diagnosis , Liver Transplantation/methods , CD4 Antigens/blood , CD8 Antigens/blood , Female , Graft Rejection/etiology , Humans , Liver Transplantation/adverse effects , Male , Middle Aged , Platelet Endothelial Cell Adhesion Molecule-1/blood , Time FactorsABSTRACT
The authors studied the concentration of CRP, sE-selectin, sP-selectin, sICAM-1, sICAM-3, sVCAM-1, sPECAM and endothelin-1 in blood serum of patients presenting with stenotic lesions of carotid arteries and undergoing various methods of carotid endarterectomy (CEAE): eversion CEAE (Group I) and CEAE using a xenopericardium patch (Group II). Within the time frame of the study, patients in both groups were found to have an elevated CRP level in the early postoperative period, having returned to the baseline values at 6 postoperative months, as well as an increase in the concentration of endothelin-1 at six months after surgery and a decrease of the sE-selectin concentration in the early postoperative period. The level of sP-selectin in Group II patients was noted to increase considerably six months after correction of stenosis. The content of sICAM-1 and sVCAM-1 did not differ in the early postoperative and baseline periods, and was noted to decrease 6 months after the operation. Group II patients demonstrated a decrease in the sPECAM concentration during postoperative day one, followed by returning to the initial values six months after CEAE. The above-mentioned biochemical markers may be used during the postoperative follow-up period for early detection and appropriate correction of endothelial dysfunction and hyperplasia of the intima of the zone of reconstruction.
Subject(s)
Biomarkers/blood , Carotid Stenosis , Endothelium, Vascular , Neointima , Postoperative Complications , Adult , Carotid Stenosis/blood , Carotid Stenosis/surgery , Early Diagnosis , Endarterectomy, Carotid/adverse effects , Endarterectomy, Carotid/methods , Endothelin-1/blood , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Female , Humans , Intercellular Adhesion Molecule-1/blood , Male , Middle Aged , Neointima/diagnosis , Neointima/etiology , Platelet Endothelial Cell Adhesion Molecule-1/blood , Postoperative Complications/blood , Postoperative Complications/diagnosis , Postoperative Period , Selectins/blood , Statistics as Topic , Vascular Cell Adhesion Molecule-1/bloodABSTRACT
OBJECTIVE: The angiogenic-antiangiogenic imbalance evident in preeclampsia (PE) may be used as a predictive tool to identify women likely to develop the clinical features in early pregnancy. METHOD: This retrospective study examined normotensive pregnant (n = 38) and preeclamptic (n = 38) HIV-infected and uninfected women to quantify sVEGFR-1 and -2 and PECAM-1 levels. RESULTS: In contrast to PECAM-1, sVEGFR-1 and -2 differed according to pregnancy type (p = 0.07; p = 0.001; p = 0.002) but not by HIV status (p = 0.68; p = 0.13; p = 0.43). CONCLUSION: Irrespective of the HIV status, we report an upregulation of sVEGFR-1 with concomitant decline of PECAM-1 and sVEGFR-2 levels in PE compared to normotensive pregnancies.
Subject(s)
HIV Infections/complications , Platelet Endothelial Cell Adhesion Molecule-1/blood , Pre-Eclampsia/virology , Vascular Endothelial Growth Factor Receptor-1/blood , Vascular Endothelial Growth Factor Receptor-2/blood , Adult , Female , HIV Infections/blood , Humans , Pre-Eclampsia/blood , Pregnancy , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. METHODS: hEPCs were isolated from peripheral blood, cultured and characterized. ß tricalcium phosphate scaffold (ßTCP, control) or 106 hEPCs loaded onto ßTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. RESULTS: On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. CONCLUSIONS: Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration.