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Endothelial Progenitor Cell
Endothelial progenitor cell (or EPC) is a term that has been applied to multiple different cell types that play roles in the regeneration of the endothelial lining of blood vessels. Outgrowth endothelial cells are an EPC subtype committed to endothelial cell formation. Despite the history and controversy, the EPC in all its forms remains a promising target of regenerative medicine research. History and controversy Developmentally, the endothelium arises in close contact with the hematopoietic system. This, and the existence of hemogenic endothelium, led to a belief and search for adult hemangioblast- or angioblast-like cells; cells which could give rise to functional vasculature in adults. The existence of endothelial progenitor cells has been posited since the mid-twentieth century, however their existence was not confirmed until the 1990s when Asahara et al. published the discovery of the first putative EPC. Recently, controversy has developed over the definition of true endothe ...
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Endothelial
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue. Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries. These cells have unique functions that include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. An impaired function can lead to serious health issues throug ...
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CD45
Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the ''PTPRC'' gene. PTPRC is also known as CD45 antigen (CD stands for cluster of differentiation), which was originally called leukocyte common antigen (LCA). Function The protein product of this gene, best known as CD45, is a member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. CD45 contains an extracellular domain, a single transmembrane segment, and two tandem intracytoplasmic catalytic domains, and thus belongs to the receptor type PTP family. CD45 is a type I transmembrane protein that is present in various isoforms on all differentiated hematopoietic cells (except erythrocytes and plasma cells). CD45 has been shown to be an essential regulator of T- and B-cell antigen receptor signaling. It functions ...
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Hemangioblasts
Hemangioblasts are the multipotent precursor cells that can differentiate into both hematopoietic and endothelial cells. In the mouse embryo, the emergence of blood islands in the yolk sac at embryonic day 7 marks the onset of hematopoiesis. From these blood islands, the hematopoietic cells and vasculature are formed shortly after. Hemangioblasts are the progenitors that form the blood islands. To date, the hemangioblast has been identified in human, mouse and zebrafish embryos. Hemangioblasts have been first extracted from embryonic cultures and manipulated by cytokines to differentiate along either hematopoietic or endothelial route. It has been shown that these pre-endothelial/pre-hematopoietic cells in the embryo arise out of a phenotype CD34 population. It was then found that hemangioblasts are also present in the tissue of post-natal individuals, such as in newborn infants and adults. Adult hemangioblast There is now emerging evidence of hemangioblasts that continue to exist ...
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ALDH
Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have been identified within the human genome. These genes participate in a wide variety of biological processes including the detoxification of exogenously and endogenously generated aldehydes. Function Aldehyde dehydrogenase is a polymorphic enzyme responsible for the oxidation of aldehydes to carboxylic acids, which leave the liver and are metabolized by the body’s muscle and heart. There are three different classes of these enzymes in mammals: class 1 (low ''K''m, cytosolic), class 2 (low ''K''m, mitochondrial), and class 3 (high ''K''m, such as those expressed in tumors, stomach, and cornea). In all three classes, constitutive and inducible forms exist. ALDH1 and ALDH2 are the most important enzymes for aldehyde oxidation, and both ...
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Von Willebrand Factor
Von Willebrand factor (VWF) () is a blood glycoprotein involved in hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic–uremic syndrome. Increased plasma levels in many cardiovascular, neoplastic, metabolic (e.g. diabetes), and connective tissue diseases are presumed to arise from adverse changes to the endothelium, and may predict an increased risk of thrombosis. Biochemistry Synthesis VWF is a large multimeric glycoprotein present in blood plasma and produced constitutively as ultra-large VWF in endothelium (in the Weibel–Palade bodies), megakaryocytes (α-granules of platelets), and subendothelial connective tissue. Structure The basic VWF monomer is a 2050-amino acid protein. Every monomer contains a number of specific domains with a specific function; elements of note are: * the D'/D3 do ...
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CXCR4
C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the ''CXCR4'' gene. The protein is a CXC chemokine receptor. Function CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 ( SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. CXCR4 is one of several chemokine co-receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are traditionally known as T-cell tropic isolates. Typically, these viruses are found late in infection. It is unclear as to whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency. CXCR4 is upregulated during the implantation window in natural and hormone replacement therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in t ...
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Angiopoietin Receptor
The angiopoietin receptors are receptors that bind angiopoietin. TIE-1 and TIE-2 comprise the cell-surface receptors that bind and are activated by the angiopoietins, (Ang1, Ang2, Ang3, Ang4). The angiopoietins are protein growth factors required for the formation of blood vessels (angiogenesis). Angiopoietins The angiopoietins are protein growth factors that regulate angiogenesis, the formation of blood vessels. In humans, three angiopoietins have been identified: Ang1, Ang2, and Ang4 (Ang 3 is the mouse ortholog of human Ang4). Ang1 and Ang4 function as agonistic or activating ligands for Tie2, whereas Ang2 and Ang3 behave as competitive antagonists. They function by binding their physiologic receptors, Tie-1 and Tie-2. These are receptor tyrosine kinases, so named because they mediate cell signals by inducing the phosphorylation of key tyrosines, thus initiating cell signalling In biology, cell signaling (cell signalling in British English) or cell communication is ...
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VEGFR2
Kinase insert domain receptor (KDR, a type IV receptor tyrosine kinase) also known as vascular endothelial growth factor receptor 2 (VEGFR-2) is a VEGF receptor. ''KDR'' is the human gene encoding it. KDR has also been designated as CD309 (cluster of differentiation 309). KDR is also known as Flk1 (Fetal Liver Kinase 1). The Q472H germline ''KDR'' genetic variant affects VEGFR-2 phosphorylation and has been found to associate with microvessel density in NSCLC. Interactions Kinase insert domain receptor has been shown to interact with SHC2, Annexin A5 and SHC1. See also * Cluster of differentiation * VEGF receptors VEGF receptors are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Also, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR), depending on alternative splicing. Inhi ... References Further reading * * * * * * * * External links * * Clusters of diff ...
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VEGFR1
Vascular endothelial growth factor receptor 1 is a protein that in humans is encoded by the ''FLT1'' gene. Function ''FLT1'' is a member of VEGF receptor gene family. It encodes a receptor tyrosine kinase which is activated by VEGF-A, VEGF-B, and placental growth factor. The sequence structure of the ''FLT1'' gene resembles that of the ''FMS'' (now ''CSF1R'') gene; hence, Yoshida et al. (1987) proposed the name FLT as an acronym for FMS-like tyrosine kinase. The ablation of VEGFR1 by chemical and genetic means has also recently been found to augment the conversion of white adipose tissue to brown adipose tissue as well as increase brown adipose angiogenesis in mice. Functional genetic variation in ''FLT1'' (rs9582036) has been found to affect non-small cell lung cancer survival. Interactions FLT1 has been shown to interact with PLCG1 and vascular endothelial growth factor B (VEGF-B). See also * VEGF receptors VEGF receptors are receptors for vascular endothel ...
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CD117
Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 (cluster of differentiation 117) or mast/stem cell growth factor receptor (SCFR). Multiple transcript variants encoding different isoforms have been found for this gene. KIT was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit. Function KIT is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. Altered forms of this receptor may be associated with some types of cancer. KIT is a receptor tyrosine kinase type III, which binds to stem cell factor , also known as "steel factor" or "c-kit ligand". When this receptor binds to stem cell factor (SCF) it forms a dimer that activates its intrinsic tyrosine kinase activity, that in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. After ...
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CD105
Endoglin (ENG) is a type I membrane glycoprotein located on cell surfaces and is part of the TGF beta receptor complex. It is also commonly referred to as CD105, END, FLJ41744, HHT1, ORW and ORW1. It has a crucial role in angiogenesis, therefore, making it an important protein for tumor growth, survival and metastasis of cancer cells to other locations in the body. Gene and expression The human endoglin gene is located on human chromosome 9 with location of the cytogenic band at 9q34.11. Endoglin glycoprotein is encoded by 39,757 bp and translates into 658 amino acids. The expression of the endoglin gene is usually low in resting endothelial cells. This, however, changes once neoangiogenesis begins and endothelial cells become active in places like tumor vessels, inflamed tissues, skin with psoriasis, vascular injury and during embryogenesis. The expression of the vascular system begins at about 4 weeks and continues after that. Other cells in which endoglin is expressed co ...
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CD31
Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31) is a protein that in humans is encoded by the ''PECAM1'' gene found on chromosome17q23.3. PECAM-1 plays a key role in removing aged neutrophils from the body. Structure PECAM-1 is a highly glycosylated protein with a mass of approximately 130 kDa. The structure of this protein was determined by molecular cloning in 1990, when it was found out that PECAM-1 has N-terminal domain with 574 amino acids, transmembrane domain with 19 amino acids and C-terminal cytoplasmic domain with 118 amino acids. The N-terminal domain consists of six extracellular Ig-like domains. Interactions PECAM-1 is a cell-cell adhesion protein which interacts with other PECAM-1 molecules through homophilic interactions or with non-PECAM-1 molecules through heterophilic interactions''.'' Homophilic interactions between PECAM-1 molecules are mediated by antiparallel interactions between extracellular ...
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