Search results for "endothelial protein C receptor"
showing 10 items of 11 documents
Comment on “Endothelial Protein C Receptor (EPCR), Protease Activated Receptor-1 (PAR-1) and Their Interplay in Cancer Growth and Metastatic Dissemin…
2019
Although the interplay between tumor progression and blood coagulation has been recognized [...]
Pathogenic lipid‐binding antiphospholipid antibodies are associated with severity of COVID‐19
2021
Abstract Background Coronavirus disease 19 (COVID‐19)–associated coagulopathy is a hallmark of disease severity and poor prognosis. The key manifestations of this prothrombotic syndrome—microvascular thrombosis, stroke, and venous and pulmonary clots—are also observed in severe and catastrophic antiphospholipid syndrome. Antiphospholipid antibodies (aPL) are detectable in COVID‐19 patients, but their association with the clinical course of COVID‐19 remains unproven. Objectives To analyze the presence and relevance of lipid‐binding aPL in hospitalized COVID‐19 patients. Methods Two cohorts of 53 and 121 patients from a single center hospitalized for PCR‐proven severe acute respiratory syndro…
Association of soluble endothelial protein C receptor plasma levels and PROCR rs867186 with cardiovascular risk factors and cardiovascular events in …
2012
Abstract Background Blood coagulation is an essential determinant of coronary artery disease (CAD). Soluble Endothelial Protein C Receptor (sEPCR) may be a biomarker of a hypercoagulable state. We prospectively investigated the relationship between plasma sEPCR levels and the risk of cardiovascular events (CVE). Methods We measured baseline sEPCR levels in 1673 individuals with CAD (521 with acute coronary syndrome [ACS] and 1152 with stable angina pectoris [SAP]) from the AtheroGene cohort. During a median follow up of 3.7 years, 136 individuals had a CVE. In addition, 891 of these CAD patients were genotyped for the PROCR rs867186 (Ser219Gly) variant. Results At baseline, sEPCR levels wer…
Integrin Alphav-beta3 on Podocytes Orchestrates Coagulation Protease Signaling through Protease-Activated Receptors
2018
Abstract Introduction Coagulation protease signaling via protease-activated receptors (PARs) is essential for maintenance of cellular homeostasis. Perturbed or aberrant activation of protease-dependent signaling via PARs propagates inflammation and pathological responses in disease models such as sepsis, neurological diseases and metabolic diseases including atherosclerosis, obesity and diabetic nephropathy (dNP). Disruption of protease-activated protein C (aPC) signaling in renal epithelial cells, i.e. podocytes, compromises adaptive endoplasmic reticulum (ER) signaling, promoting maladaptive ER-stress and ultimately dysfunction of the glomerular filtration barrier and dNP. While these res…
Role of the protein C receptor in cancer progression
2014
The hemostatic system plays pleiotropic roles in cancer progression by shaping the tumor microenvironment and metastatic niches through thrombin-dependent fibrin deposition and platelet activation. Expanding experimental evidence implicates coagulation protease receptors expressed by tumor cells as additional players that directly influence tumor biology. Pro-angiogenic G protein-coupled signaling of TF through protease activated receptor 2 and regulation of tumor cell and vascular integrins through ligation by alternative spliced TF are established pathways driving tumor progression. Our recent work shows that the endothelial protein C receptor (EPCR), a stem cell marker in hematopoietic, …
Tissue factor at the crossroad of coagulation and cell signaling
2018
The tissue factor (TF) pathway plays a central role in hemostasis and thrombo-inflammatory diseases. Although structure-function relationships of the TF initiation complex are elucidated, new facets of the dynamic regulation of TF?s activities on cells continue to emerge. Cellular pathways that render TF non-coagulant participate in signaling of distinct TF complexes with associated proteases through the protease-activated receptor (PAR) family of G-protein coupled receptors. Additional coreceptors, including the endothelial protein C receptor (EPCR) and integrins, confer signaling specificity by directing subcellular localization and trafficking. We here review how TF is switchedbetween it…
Lipid presentation by the protein C receptor links coagulation with autoimmunity.
2021
A lipid-protein autoimmunity target Several autoimmune diseases, including systemic lupus erythematosus and primary antiphospholipid syndrome, are characterized by the presence of antiphospholipid antibodies (aPLs). These molecules can activate the complement and coagulation cascades, which contributes to pathologies such as thrombosis, stroke, and pregnancy complications. Müller-Calleja et al. found that endothelial protein C receptor (EPCR) in complex with lysobisphosphatidic acid (LBPA) is the cell-surface target for aPL and mediates its internalization (see the Perspective by Kaplan). aPL binding to EPCR-LBPA resulted in the activation of tissue factor–mediated coagulation and interfero…
EPCR Guides Hematopoietic Stem Cells Homing to the Bone Marrow Independently of Niche Clearance
2016
Abstract Bone marrow (BM) homing and lodgment of long-term repopulating hematopoietic stem cells (LT-HSCs) are active and essential first steps during embryonic development and in clinical stem cell transplantation. Rare, BM LT-HSCs endowed with the highest self-renewal and durable repopulation potential, functionally express the anticoagulant endothelial protein C receptor (EPCR) and PAR1. In addition to coagulation and inflammation, EPCR-PAR1 signaling independently controls a BM LT-HSC retention-release switch via regulation of nitric oxide (NO) production within LT-HSCs. EPCR+ LT-HSCs are maintained in thrombomodulin+ (TM) periarterial BM microenvironments via production of activated pr…
PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells
2015
Retention of long-term repopulating hematopoietic stem cells (LT-HSCs) in the bone marrow is essential for hematopoiesis and for protection from myelotoxic injury. We report that signaling cascades that are traditionally viewed as coagulation related also control retention of endothelial protein C receptor-positive (EPCR(+)) LT-HSCs in the bone marrow and their recruitment to the blood via two pathways mediated by protease activated receptor 1 (PAR1). Thrombin-PAR1 signaling induces nitric oxide (NO) production, leading to EPCR shedding mediated by tumor necrosis factor-α-converting enzyme (TACE), enhanced CXCL12-CXCR4-induced motility and rapid stem and progenitor cell mobilization. Conver…
Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling
2016
The common developmental origin of endothelial and hematopoietic cells is manifested by coexpression of several cell surface receptors. Adult murine bone marrow (BM) long-term repopulating hematopoietic stem cells (LT-HSCs), endowed with the highest repopulation and self-renewal potential, express endothelial protein C receptor (EPCR), which is used as a marker to isolate them. EPCR/protease-activated receptor-1 (PAR1) signaling in endothelial cells has anticoagulant and anti-inflammatory roles, while thrombin/PAR1 signaling induces coagulation and inflammation. Recent studies define two new PAR1-mediated signaling cascades that regulate EPCR(+) LT-HSC BM retention and egress. EPCR/PAR1 sig…