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Blood Aug 2016Thiol isomerases are multifunctional enzymes that influence protein structure via their oxidoreductase, isomerase, and chaperone activities. These enzymes localize at... (Review)
Review
Thiol isomerases are multifunctional enzymes that influence protein structure via their oxidoreductase, isomerase, and chaperone activities. These enzymes localize at high concentrations in the endoplasmic reticulum of all eukaryotic cells where they serve an essential function in folding nascent proteins. However, thiol isomerases can escape endoplasmic retention and be secreted and localized on plasma membranes. Several thiol isomerases including protein disulfide isomerase, ERp57, and ERp5 are secreted by and localize to the membranes of platelets and endothelial cells. These vascular thiol isomerases are released following vessel injury and participate in thrombus formation. Although most of the activities of vascular thiol isomerases that contribute to thrombus formation are yet to be defined at the molecular level, allosteric disulfide bonds that are modified by thiol isomerases have been described in substrates such as αIIbβ3, αvβ3, GPIbα, tissue factor, and thrombospondin. Vascular thiol isomerases also act as redox sensors. They respond to the local redox environment and influence S-nitrosylation of surface proteins on platelets and endothelial cells. Despite our rudimentary understanding of the mechanisms by which thiol isomerases control vascular function, the clinical utility of targeting them in thrombotic disorders is already being explored in clinical trials.
Topics: Animals; Blood Vessels; Hemostasis; Humans; Models, Biological; Oxidation-Reduction; Protein Disulfide-Isomerases; Thrombosis
PubMed: 27357699
DOI: 10.1182/blood-2016-04-636456 -
Journal of Thrombosis and Haemostasis :... Mar 2016Collagens mediate essential hemostasis by maintaining the integrity and stability of the vascular wall. Imbalanced turnover of collagens by uncontrolled formation and/or... (Review)
Review
Collagens mediate essential hemostasis by maintaining the integrity and stability of the vascular wall. Imbalanced turnover of collagens by uncontrolled formation and/or degradation may result in pathologic conditions such as fibrosis. Thickening of the vessel wall because of accumulation of collagens may lead to arterial occlusion or thrombosis. Thinning of the wall because of collagen degradation or deficiency may lead to rupture of the vessel wall or aneurysm. Preventing excessive hemorrhage or thrombosis relies on collagen-mediated actions. Von Willebrand factor, integrins and glycoprotein VI, as well as clotting factors, can bind collagen to restore normal hemostasis after trauma. This review outlines the essential roles of collagens in mediating hemostasis, with a focus on collagens types I, III, IV, VI, XV, and XVIII.
Topics: Animals; Basement Membrane; Blood Coagulation; Blood Platelets; Blood Vessels; Collagen; Humans; Megakaryocytes; Platelet Adhesiveness; Platelet Aggregation; Signal Transduction; Vascular Diseases
PubMed: 26749406
DOI: 10.1111/jth.13249 -
Genesis (New York, N.Y. : 2000) Jul 2019Formation of the vasculature is an essential developmental process, delivering oxygen and nutrients to support cellular processes needed for tissue growth and... (Review)
Review
Formation of the vasculature is an essential developmental process, delivering oxygen and nutrients to support cellular processes needed for tissue growth and maturation. Retinoic acid (RA) and its downstream signaling pathway is vital for normal pre- and post-natal development, playing key roles in the specification and formation of many organs and tissues. Here, we review the role of RA in blood and lymph vascular development, beginning with embryonic yolk sac vasculogenesis and remodeling and discussing RA's organ-specific roles in angiogenesis and vessel maturation. In particular, we highlight the multi-faceted role of RA signaling in CNS vascular development and acquisition of blood-brain barrier properties.
Topics: Animals; Blood Vessels; Humans; Lymphatic Vessels; Neovascularization, Physiologic; Signal Transduction; Tretinoin
PubMed: 30801891
DOI: 10.1002/dvg.23287 -
Experimental Cell Research May 2015Acting through cell surface receptors, “extracellular” lysophosphatidic acid (LPA) influences cell growth, differentiation, apoptosis and development in a wide... (Review)
Review
Acting through cell surface receptors, “extracellular” lysophosphatidic acid (LPA) influences cell growth, differentiation, apoptosis and development in a wide spectrum of settings [–5]. Within the vasculature, smooth muscle cells [6, 7], endothelial cells [8] and platelets [9, 10] display notable responses to LPA [11, 12], which likely regulate blood vessel development and contribute to vascular pathology. The bioactive effects of LPA are mediated by a family of G-protein coupled receptors with at least six members (termed LPA that are encoded by the genes in humans and in mice) [–3]. LPA may also serve as a ligand for the receptor for advanced glycation end products (RAGE) [13]. This review summarizes evidence to support a role for LPA signaling in vascular biology based on studies of LPA receptors and enzymes that produce or metabolize the lipid (Figure 1).
Topics: Animals; Atherosclerosis; Blood Vessels; Cell Communication; Humans; Lysophospholipids; Phosphoric Diester Hydrolases; Receptors, Lysophosphatidic Acid; Signal Transduction
PubMed: 25825155
DOI: 10.1016/j.yexcr.2015.03.016 -
Stem Cells Translational Medicine Mar 2022The vascular wall is comprised of distinct layers controlling angiogenesis, blood flow, vessel anchorage within organs, and cell and molecule transit between blood and... (Review)
Review
The vascular wall is comprised of distinct layers controlling angiogenesis, blood flow, vessel anchorage within organs, and cell and molecule transit between blood and tissues. Moreover, some blood vessels are home to essential stem-like cells, a classic example being the existence in the embryo of hemogenic endothelial cells at the origin of definitive hematopoiesis. In recent years, microvascular pericytes and adventitial perivascular cells were observed to include multi-lineage progenitor cells involved not only in organ turnover and regeneration but also in pathologic remodeling, including fibrosis and atherosclerosis. These perivascular mesodermal elements were identified as native forerunners of mesenchymal stem cells. We have presented in this brief review our current knowledge on vessel wall-associated tissue remodeling cells with respect to discriminating phenotypes, functional diversity in health and disease, and potential therapeutic interest.
Topics: Endothelial Cells; Humans; Mesenchymal Stem Cells; Pericytes; Peripheral Blood Stem Cells; Stem Cells
PubMed: 35641167
DOI: 10.1093/stcltm/szab001 -
Nature Jun 2022The lineage and developmental trajectory of a cell are key determinants of cellular identity. In the vascular system, endothelial cells (ECs) of blood and lymphatic...
The lineage and developmental trajectory of a cell are key determinants of cellular identity. In the vascular system, endothelial cells (ECs) of blood and lymphatic vessels differentiate and specialize to cater to the unique physiological demands of each organ. Although lymphatic vessels were shown to derive from multiple cellular origins, lymphatic ECs (LECs) are not known to generate other cell types. Here we use recurrent imaging and lineage-tracing of ECs in zebrafish anal fins, from early development to adulthood, to uncover a mechanism of specialized blood vessel formation through the transdifferentiation of LECs. Moreover, we demonstrate that deriving anal-fin vessels from lymphatic versus blood ECs results in functional differences in the adult organism, uncovering a link between cell ontogeny and functionality. We further use single-cell RNA-sequencing analysis to characterize the different cellular populations and transition states involved in the transdifferentiation process. Finally, we show that, similar to normal development, the vasculature is rederived from lymphatics during anal-fin regeneration, demonstrating that LECs in adult fish retain both potency and plasticity for generating blood ECs. Overall, our research highlights an innate mechanism of blood vessel formation through LEC transdifferentiation, and provides in vivo evidence for a link between cell ontogeny and functionality in ECs.
Topics: Animal Fins; Animals; Blood Vessels; Cell Lineage; Cell Transdifferentiation; Endothelial Cells; Lymphatic Vessels; Zebrafish
PubMed: 35614218
DOI: 10.1038/s41586-022-04766-2 -
Neuroscience Bulletin Jun 2019Cerebral pericytes are perivascular cells that stabilize blood vessels. Little is known about the plasticity of pericytes in the adult brain in vivo. Recently, using... (Review)
Review
Cerebral pericytes are perivascular cells that stabilize blood vessels. Little is known about the plasticity of pericytes in the adult brain in vivo. Recently, using state-of-the-art technologies, including two-photon microscopy in combination with sophisticated Cre/loxP in vivo tracing techniques, a novel role of pericytes was revealed in vascular remodeling in the adult brain. Strikingly, after pericyte ablation, neighboring pericytes expand their processes and prevent vascular dilatation. This new knowledge provides insights into pericyte plasticity in the adult brain.
Topics: Animals; Brain; Brain Diseases; Capillaries; Cellular Microenvironment; Diabetic Retinopathy; Endothelial Cells; Humans; Pericytes; Vascular Remodeling
PubMed: 30367336
DOI: 10.1007/s12264-018-0296-5 -
Matrix Biology : Journal of the... Jan 2019Thrombospondin-4 (TSP-4) belongs to the thrombospondin protein family that consists of five highly homologous members. A number of novel functions have been recently... (Review)
Review
Thrombospondin-4 (TSP-4) belongs to the thrombospondin protein family that consists of five highly homologous members. A number of novel functions have been recently assigned to TSP-4 in cardiovascular and nervous systems, inflammation, cancer, and the motor unit, which have attracted attention to this extracellular matrix (ECM) protein. These newly discovered functions set TSP-4 apart from other thrombospondins. For example, TSP-4 promotes angiogenesis while other TSPs either prevent it or have no effect on new blood vessel growth; TSP-4 reduces fibrosis and collagen production while TSP-1 and TSP-2 promote fibrosis in several organs; unlike other TSPs, TSP-4 appears to have some structural functions in ECM. The current information about TSP-4 functions in different organs and physiological systems suggests that this evolutionary conserved protein is a major regulator of the extracellular matrix (ECM) organization and production and tissue remodeling during the embryonic development and response to injury. In this review article, we summarize the properties and functions of TSP-4 and discuss its role in tissue remodeling.
Topics: Blood Vessels; Extracellular Matrix; Extracellular Matrix Proteins; Fibrosis; Gene Expression Regulation, Developmental; Humans; Neovascularization, Pathologic; Thrombospondin 1; Thrombospondins
PubMed: 29138119
DOI: 10.1016/j.matbio.2017.11.006 -
Cold Spring Harbor Perspectives in... Jul 2018Blood vessels are essential for the distribution of oxygen, nutrients, and immune cells, as well as the removal of waste products. In addition to this conventional role... (Review)
Review
Blood vessels are essential for the distribution of oxygen, nutrients, and immune cells, as well as the removal of waste products. In addition to this conventional role as a versatile conduit system, the endothelial cells forming the innermost layer of the vessel wall also possess important signaling capabilities and can control growth, patterning, homeostasis, and regeneration of the surrounding organ. In the skeletal system, blood vessels regulate developmental and regenerative bone formation as well as hematopoiesis by providing vascular niches for hematopoietic stem cells. Here we provide an overview of blood vessel architecture, growth and properties in the healthy, aging, and diseased skeletal system.
Topics: Aging; Blood Vessels; Bone and Bones; Endothelial Cells; Endothelium, Vascular; Fibroblast Growth Factors; Fracture Healing; Humans; Neovascularization, Physiologic; Osteogenesis; Osteonecrosis; Osteoporosis; Receptors, Notch; Signal Transduction; Transcription Factors; Vascular Endothelial Growth Factor A
PubMed: 28893838
DOI: 10.1101/cshperspect.a031559 -
Cellular and Molecular Life Sciences :... Mar 2018Vascular stem/progenitor cells (VSCs) are an important source of all types of vascular cells needed to build, maintain, repair, and remodel blood vessels. VSCs,... (Review)
Review
Vascular stem/progenitor cells (VSCs) are an important source of all types of vascular cells needed to build, maintain, repair, and remodel blood vessels. VSCs, therefore, play critical roles in the development, normal physiology, and pathophysiology of numerous diseases. There are four major types of VSCs, including endothelial progenitor cells (EPCs), smooth muscle progenitor cells (SMPCs), pericytes, and mesenchymal stem cells (MSCs). VSCs can be found in bone marrow, circulating blood, vessel walls, and other extravascular tissues. During the past two decades, considerable progress has been achieved in the understanding of the derivation, surface markers, and differentiation of VSCs. Yet, the mechanisms regulating their functions and maintenance under normal and pathological conditions, such as in eye diseases, remain to be further elucidated. Owing to the essential roles of blood vessels in human tissues and organs, understanding the functional properties and the underlying molecular basis of VSCs is of critical importance for both basic and translational research.
Topics: Animals; Cell Differentiation; Humans; Mesenchymal Stem Cells; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neovascularization, Physiologic; Pericytes; Signal Transduction; Stem Cells
PubMed: 28956069
DOI: 10.1007/s00018-017-2662-2