Search results for "Vascular"
showing 10 items of 10708 documents
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…
Paraoxonase-2 regulates coagulation activation through endothelial tissue factor
2017
Oxidative stress and inflammation of the vessel wall contribute to prothrombotic states. The antioxidative protein paraoxonase-2 (PON2) shows reduced expression in human atherosclerotic plaques and endothelial cells in particular. Supporting a direct role for PON2 in cardiovascular diseases, Pon2 deficiency in mice promotes atherogenesis through incompletely understood mechanisms. Here, we show that deregulated redox regulation in Pon2 deficiency causes vascular inflammation and abnormalities in blood coagulation. In unchallenged Pon2-/- mice, we find increased oxidative stress and endothelial dysfunction. Bone marrow transplantation experiments and studies with endothelial cells provide ev…
Microparticles harbouring Sonic hedgehog morphogen improve the vasculogenesis capacity of endothelial progenitor cells derived from myocardial infarc…
2019
Aims Endothelial progenitor cells (EPC) play a role in endothelium integrity maintenance and regeneration. Decreased numbers of EPC or their impaired function correlates with an increase in cardiovascular events. Thus, EPC are important predictors of cardiovascular mortality and morbidity. Microparticles carrying Sonic hedgehog (Shh) morphogen (MPShh+) trigger pro-angiogenic responses, both in endothelial cells and in ischaemic rodent models. Here, we propose that MPShh+ regulates EPC function, thus enhancing vasculogenesis, and correcting the defects in dysfunctional EPC obtained from acute myocardial infarction (AMI) patients. Methods and results The mechanisms underlying Shh pathway func…
GAS6
2017
Venous thrombosis is determined by the recruitment of monocytes and neutrophils to the inflamed endothelium and is primarily influenced by the plasmatic coagulation system.1 Monocyte tissue factor (TF) was identified as the causative trigger for intraluminal fibrin formation and thrombus load in the inferior vena cava (IVC) stenosis model, resembling human deep vein thrombosis.1 Although monocyte TF is prothrombotic, the TF expressed by activated endothelial cells triggers proinflammatory protease-activated receptor signaling pathways.2,3 See accompanying article on page 1315 In the past years, GAS6 (growth arrest–specific gene-6) was described as a major regulatory protein of prothrombotic…
Monitoring of rheologic variables during postoperative high-dose brachytherapy for uterine cancer.
2004
Oxygenation of tumor tissue has recently been assed an important prerequisite for the effectiveness of radiotherapy in cervical cancer. Hyperviscosity is a common phenomenon in malignancy and a cause of reduced oxygen transport capacity that would favour tissue hypoxia. Hemorheological variables were serially tested preoperatively, during four cycles of fractionated adjuvant IR192 HDR after loading radiation (HDR-AL) of the vaginal vault (weekly intervals), and 6 months postoperatively in patients with cervical (n=12) and endometrial cancer (n=26). Women who were scheduled for benign tumor surgery served as controls (n=29). Preoperatively, in cervical and endometrial cancer patients, mean …
miRNA as New Regulatory Mechanism of Estrogen Vascular Action
2018
The beneficial effects of estrogen on the cardiovascular system have been reported extensively. In fact, the incidence of cardiovascular diseases in women is lower than in age-matched men during their fertile stage of life, a benefit that disappears after menopause. These sex-related differences point to sexual hormones, mainly estrogen, as possible cardiovascular protective factors. The regulation of vascular function by estrogen is mainly related to the maintenance of normal endothelial function and is mediated by both direct and indirect gene transcription through the activity of specific estrogen receptors. Some of these mechanisms are known, but many remain to be elucidated. In recent …
Advances in Understanding the Molecular Basis of the Mediterranean Diet Effect
2018
Posted with permission from the Annual Review of Food Science and Technology, Volume 9 by Annual Reviews, http://www.annualreviews.org. Increasingly, studies showing the protective effects of the Mediterranean diet (MedDiet) on different diseases (cardiovascular, diabetes, some cancers, and even total mortality and aging indicators) are being published. The scientific evidence level for each outcome is variable, and new studies are needed to better understand the molecular mechanisms whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases but also discussing other relat…
Annexin A2-Mediated Plasminogen Activation in Endothelial Cells Contributes to the Proangiogenic Effect of Adenosine A2A Receptors
2021
Adenosine A2A receptor mediates the promotion of wound healing and revascularization of injured tissue, in healthy and animals with impaired wound healing, through a mechanism depending upon tissue plasminogen activator (tPA), a component of the fibrinolytic system. In order to evaluate the contribution of plasmin generation in the proangiogenic effect of adenosine A2A receptor activation, we determined the expression and secretion of t-PA, urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) and annexin A2 by human dermal microvascular endothelial cells stimulated by the selective agonist CGS-21680. The plasmin generation was assayed through an enzymatic assay a…
CNS Macrophages Control Neurovascular Development via CD95L.
2017
The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina. Furthermore, we identify CNS macrophages as the main source of CD95L, and macrophage-specific del…
Visualizing the spatiotemporal map of Rac activation in bovine aortic endothelial cells under laminar and disturbed flows.
2017
Disturbed flow can eliminate the alignment of endothelial cells in the direction of laminar flow, and significantly impacts on atherosclerosis in collateral arteries near the bifurcation and high curvature regions. While shear stress induced Rac polarity has been shown to play crucial roles in cell polarity and migration, little is known about the spatiotemporal map of Rac under disturbed flow, and the mechanism of flow-induced cell polarity still needs to be elucidated. In this paper, disturbed flow or laminar flow with 15 dyn/cm2 of average shear stress was applied on bovine aortic endothelial cells (BAECs) for 30 minutes. A genetically-encoded PAK-PBD-GFP reporter was transfected into BA…