Platelet-endothelial cell adhesion molecule-1 and CD146: soluble levels and in situ expression of cellular adhesion molecules implicated in the cohesion of endothelial cells in idiopathic inflammatory myopathies.

Objective: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases characterized by chronic inflammation of muscles. We investigated the role of cellular adhesion molecules implicated in the cohesion of endothelial cells in IIM.

Methods: In 22 patients with IIM we investigated plasma concentrations of soluble junctional adhesion molecules [platelet-endothelial cell adhesion molecule (sPECAM-1) and sCD146] and cellular adhesion molecules [sP-selectin, sE-selectin, intercellular adhesion molecule (sICAM-1), and vascular cell adhesion molecule (sVCAM-1)] implicated in leukocyte/endothelial cell interactions.

Thrombin-induced endothelial microparticle generation: identification of a novel pathway involving ROCK-II activation by caspase-2.

Thrombin exerts pleiotropic effects on endothelial cells, including the release of microparticles (EMPs) that disseminate and exchange information with vascular cells. Nevertheless, the mechanisms leading to their generation are not elucidated. We performed microarray analysis to identify genes involved in EMP release by the endothelial cell line HMEC-1 in response to thrombin.

High urokinase expression contributes to the angiogenic properties of endothelial cells derived from circulating progenitors.

Endothelial progenitor cells (EPC) display a unique ability to repair vascular injury and promote neovascularization although the underlying molecular mechanisms remain poorly understood. Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play a critical role in cell migration and angiogenesis by facilitating proteolysis of extracellular matrix. The aim of the present study was to characterize the uPA/uPAR-dependent proteolytic potential of EPC outgrown from human umbilical cord blood and to analyze its contribution to their angiogenic properties in vitro.

The first assessment of soluble CD146 in women with unexplained pregnancy loss. A new insight?

The mechanisms responsible for pregnancy loss have not all been elucidated. CD146 is a cell adhesion molecule involved in the control of both endothelium integrity and intermediate trophoblast invasiveness, two potential key features in the pathogenesis of pregnancy loss. As CD146 is detectable as a soluble form in the plasma (sCD146), we investigated sCD146 plasma levels in women with a history of pregnancy loss.

Presence of endothelial progenitor cells, distinct from mature endothelial cells, within human CD146+ blood cells.

CD146 is an adhesion molecule present on endothelial cells throughout the vascular tree. CD146 is also expressed by circulating endothelial cells (CECs) widely considered to be mature endothelial cells detached from injured vessels. The discovery of circulating endothelial progenitor cells (EPCs) originating from bone marrow prompted us to investigate whether CD146 circulating cells could also contains EPCs.

Increased expression of CD146, a new marker of the endothelial junction in active inflammatory bowel disease.

Background: Crohn's disease (CD) and ulcerative colitis (UC), the 2 major forms of inflammatory bowel diseases (IBD), have been associated with disturbances in vascular physiology, including permeability and angiogenesis, that are in part regulated by the endothelial intercellular junctions. These junctions are composed of several adhesion molecules including the platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) and the more recently described CD146 (S-Endo1 Ag, MUC18).

Aim: To study the expression of tissue and soluble form of CD146 in patients with CD or UC in relation to disease activity and location.

Role of reactive oxygen species and p38 MAPK in the induction of the pro-adhesive endothelial state mediated by IgG from patients with anti-phospholipid syndrome.

The association of the presence of anti-phospholipid antibodies (aPL) with thrombosis characterizes the anti-phospholipid syndrome (APS). The activation of the endothelium is a key event in the establishment of the thrombophilic state. However, the intracellular mechanisms leading to endothelial dysfunction are not fully elucidated.

Circulating endothelial cells. Biomarker of vascular disease.

Recent research has recognised new populations of non-hematopoietic cells in the blood. One of these, circulating endothelial cells (CECs), often defined by the expression of membrane glycoprotein CD146, are rarely found in the blood in health, but raised numbers are present in a wide variety of human conditions, including inflammatory, immune, infectious, neoplastic and cardiovascular disease, and seem likely to be evidence of profound vascular insult. An additional population are endothelial progenitor cells, defined by the co-expression of endothelial and immaturity cell surface molecules and also by the ability to form colonies in vitro.

Tubular CD146 expression in nephropathies is related to chronic renal failure.

Background: CD146, a member of the immunoglobulin superfamily, is mainly expressed at the endothelial junction. The soluble form of CD146 is increased in the serum of patients with chronic renal failure. The aim of the study was to investigate CD146 expression on biopsies of normal kidney and nephropathies.

Circulating endothelial cells: realities and promises in vascular disorders.

Endothelial contribution to human vascular disorders is difficult to investigate, owing to the paucity of non-invasive methods and of specific endothelial markers . Circulating endothelial cells (CECs) might be used asa surrogate non-invasive marker for the study of vascular alterations. To address this problem, we produced an antibody against the endothelial molecule CD126 (S-Endol) and developed, in the nineties, an original and sensitive immunomagnetic separation assay.

Heterogeneity of anti-beta2-glycoprotein I antibodies. A factor of variability in test results.

The aim of this study was to evaluate the heterogeneity of IgGanti-beta2-glycoprotein I antibodies (IgG-abeta2GPI) as regarding their reactivity pattern against different sources of human beta2 GPI, their avidity and their association with clinical events of antiphospholipid syndrome (APS). Three thousand six hundred and eighty-four consecutive patient sera were routinely tested for IgGabeta2 GPI over 1 year using an in-house ELISA with 2 different commercial preparations of human purified beta2GPI. Of the 340 sera found positive, all those clinically documented were included in this study; 61 were positive with only one preparation (S1) and 59 with both (S2).

Comparative analysis of NK cell subset distribution in normal and lymphoproliferative disease of granular lymphocyte conditions.

We have characterized the heterogeneity of human blood NK cell subsets defined by expression of KIR, lectin like receptors and NK cell differentiation markers within a cohort of 51 healthy Caucasian individuals. High inter-individual variability in cell surface expression of most NK cell markers is observed. Range values defining NK cell subsets in healthy donors were further used as references to characterize 14 patients with NK-type lymphoproliferative disease of granular lymphocytes (NK-LDGL).

Circulating endothelial cell count as a diagnostic marker for non-ST-elevation acute coronary syndromes.

Background: Shedding of endothelial cells from damaged endothelium into the blood occurs in a variety of vascular disorders. The purpose of this study was to evaluate the utility of circulating endothelial cell (CEC) count as a diagnostic marker of non-ST-elevation acute coronary syndromes (ACSs).

Methods And Results: CEC counts were determined immediately (H0), 4 hours (H4), and 8 hours (H8) after admission in 60 patients with documented non-ST-elevation ACS and 40 control patients with no evidence of coronary artery disease.

P-cresol, a uremic retention solute, alters the endothelial barrier function in vitro.

Patients with chronic renal failure (CRF) exhibit endothelial dysfunction, which may involve uremic retention solutes that accumulate in blood and tissues. In this study, we investigated the in vitro effect of the uremic retention solute p-cresol on the barrier function of endothelial cells (HUVEC). P-cresol was tested at concentrations found in CRF patients, and since p-cresol is protein-bound, experiments were performed with and without physiological concentration of human albumin (4 g/dl).

Cell adhesion molecules as a marker reflecting the reduction of endothelial activation induced by glucocorticoids.

In vitro, steroids down-regulate the expression of cell adhesion molecules (CAMs) in endothelial cells stimulated by lipopolysaccharide. Low-dose hydrocortisone is a new treatment of patients with septic shock, a state that is characterized by an endothelial injury. The aim of the present study was to investigate whether the plasma levels of soluble CAMs, reflecting in vivo endothelial activation, could be modulated in patients with septic shock treated by hydrocortisone.

Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome.

The antiphospholipid syndrome (APS) refers to persistent anti-phospholipid antibodies (aPL) associated with thrombotic and/or obstetrical complications. The endothelial cell is a target of aPL which can induce a procoagulant and proinflammatory endothelial phenotype, as reported both in vivo and in vitro. Microparticle production is a hallmark of cell activation.

Homocysteine modulates the proteolytic potential of human vascular endothelial cells.

Pathological levels of homocysteine induce a metalloproteinase-dependent degradation of the elastic structures in arterial wall. This elastolytic process is preferentially localized toward the internal elastic laminae and in the first layers of the media, suggesting endothelium could participate in extracellular matrix degradation induced by homocysteine. Therefore, we studied the effects of homocysteine on proteolytic potential of endothelial cells.

Soluble CD146, a novel endothelial marker, is increased in physiopathological settings linked to endothelial junctional alteration.

CD146, a novel cell adhesion molecule localized at the endothelial junction, is involved in the control of cell-cell cohesion. It is found as a soluble form in conditioned medium of cultured endothelial cells. We developed an ELISA and report for the first time the presence of a soluble form of CD146 (sCD146) in the plasma of healthy subjects.

Circulating microparticles: a marker of procoagulant state in normal pregnancy and pregnancy complicated by preeclampsia or intrauterine growth restriction.

In the present study, we explored the microparticles involved in the control of hemostatic equilibrium, i.e microparticles originating from platelet, endothelial cells and total MP defined as annexin V positive microparticles. Our aim was to analyze the level and procoagulant activity of these microparticles in normal pregnancy and pregnancies complicated with preeclampsia or isolated intrauterine growth restriction.

Type 1 and type 2 diabetic patients display different patterns of cellular microparticles.

The development of vasculopathies in diabetes involves multifactorial processes including pathological activation of vascular cells. Release of microparticles by activated cells has been reported in diseases associated with thrombotic risk, but few data are available in diabetes. The aim of the present work was to explore the number and the procoagulant activity of cell-derived microparticles in type 1 and 2 diabetic patients.

Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity.

In the present study we investigated whether endothelial microparticles (EMPs) can bind to monocytic THP-1 cells and modulate their procoagulant properties. Using flow cytometry, we demonstrated that EMPs express adhesive receptors similar to those expressed by activated endothelial cells. Expression of endothelial antigens by THP-1 cells incubated with EMP was shown by immunoperoxidase staining and flow cytometry using antibodies directed against E-selectin, VCAM-1, and endoglin.

Systemic endothelial activation is greater in septic than in traumatic-hemorrhagic shock but does not correlate with endothelial activation in skin biopsies.

Objective: Sepsis and severe trauma result in endothelial activation and damage. The activated endothelium expresses adhesion receptors that control leukocyte trafficking. After activation, some adhesion molecules are also released into plasma as soluble forms.