Angiogenesis is the process of the formation of new blood vessels from pre-existing vascular structures, which is needed for oxygenation of - and providing nutrients to - expanding tissue. Angiogenesis takes place through different modes of action. Coalescent angiogenesis is a mode of angiogenesis where vessels coalesce or fuse to increase blood circulation. This process transforms an inefficient net structure into a more efficient treelike structure. It is the opposite of intussusceptive angiogenesis, which is where vessels split to form new vessels.
While the most studied mode of angiogenesis is sprouting angiogenesis, several different modes of angiogenesis have been described. [1] Among these are intussusceptive angiogenesis or splitting angiogenesis, [2] [3] vessel cooption, and vessel elongation. A novel form of angiogenesis is the process called ‘’’coalescent angiogenesis’’’, which is the opposite of intussusceptive angiogenesis. [4] [5] This mode of angiogenesis was reported from studies of long-term time-lapse microscopy in the vasculature of the chick chorioallantoic membrane (CAM), where this novel non-sprouting mode for vessel generation was observed.
Specifically, isotropic capillary meshes enclosing tissue islands evolve into preferred flow pathways consisting of larger blood vessels transporting more blood in a faster pace. These preferential flow pathways progressively enlarge by coalescence of capillaries and elimination of internal tissue pillars, in a fast time frame of hours. This way coalescent angiogenesis is the reverse of intussusceptive angiogenesis. Concomitantly, less perfused segments of the vasculature regress. An initially mesh-like capillary network is remodelled into a tree structure, while conserving vascular wall components and maintaining blood flow. Coalescent angiogenesis, thus, describes the remodelling of an initial hemodynamically inefficient mesh structure, into a hierarchical tree structure that provides efficient convective transport, allowing for the rapid expansion of the vasculature with maintained blood supply and function during development.
Vascular fusion was initially described to happen during the formation of the dorsal aorta. [6] All research presented has been derived from embryo development studies. It is unknown whether coalescent angiogenesis has extended out of the domain of embryology. In any case, it has been overlooked in the field of cancer research and it is currently only assumed to play a role in the formation of tumor vasculature. [5]
A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the site of the exchange of many substances from the surrounding interstitial fluid, and they convey blood from the smallest branches of the arteries (arterioles) to those of the veins (venules). Other substances which cross capillaries include water, oxygen, carbon dioxide, urea, glucose, uric acid, lactic acid and creatinine. Lymph capillaries connect with larger lymph vessels to drain lymphatic fluid collected in microcirculation.
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and splitting, but processes such as coalescent angiogenesis, vessel elongation and vessel cooption also play a role. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease.
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.
Mural cells are the vascular smooth muscle cells (vSMCs), and pericytes, of the microcirculation. Both types are in close contact with the endothelial cells lining the capillaries, and are important for vascular development and stability. Mural cells are involved in the formation of normal vasculature and are responsive to factors including platelet-derived growth factor B (PDGFB) and vascular endothelial growth factor (VEGF). The weakness and disorganization of tumor vasculature is partly due to the inability of tumors to recruit properly organized mural cells.
Pericytes are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries throughout the body. Pericytes are embedded in the basement membrane of blood capillaries, where they communicate with endothelial cells by means of both direct physical contact and paracrine signaling. The morphology, distribution, density and molecular fingerprints of pericytes vary between organs and vascular beds. Pericytes help to maintain homeostatic and hemostatic functions in the brain, one of the organs with higher pericyte coverage, and also sustain the blood–brain barrier. These cells are also a key component of the neurovascular unit, which includes endothelial cells, astrocytes, and neurons. Pericytes have been postulated to regulate capillary blood flow and the clearance and phagocytosis of cellular debris in vitro. Pericytes stabilize and monitor the maturation of endothelial cells by means of direct communication between the cell membrane as well as through paracrine signaling. A deficiency of pericytes in the central nervous system can cause increased permeability of the blood–brain barrier.
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical drugs or diet.
Vasculogenesis is the process of blood vessel formation, occurring by a de novo production of endothelial cells. It is sometimes paired with angiogenesis, as the first stage of the formation of the vascular network, closely followed by angiogenesis.
Intussusceptive angiogenesis also known as splitting angiogenesis, is a type of angiogenesis, the process whereby a new blood vessel is created. By intussusception a new blood vessel is created by splitting of an existing blood vessel in two. Intussusception occurs in normal development as well as in pathologic conditions involving wound healing, tissue regeneration, inflammation as colitis or myocarditis, lung fibrosis, and tumors amongst others.
Neovascularization is the natural formation of new blood vessels, usually in the form of functional microvascular networks, capable of perfusion by red blood cells, that form to serve as collateral circulation in response to local poor perfusion or ischemia.
The hypophyseal portal system is a system of blood vessels in the microcirculation at the base of the brain, connecting the hypothalamus with the anterior pituitary. Its main function is to quickly transport and exchange hormones between the hypothalamus arcuate nucleus and anterior pituitary gland. The capillaries in the portal system are fenestrated which allows a rapid exchange between the hypothalamus and the pituitary. The main hormones transported by the system include gonadotropin-releasing hormone, corticotropin-releasing hormone, growth hormone–releasing hormone, and thyrotropin-releasing hormone.
Endothelial stem cells (ESCs) are one of three types of stem cells found in bone marrow. They are multipotent, which describes the ability to give rise to many cell types, whereas a pluripotent stem cell can give rise to all types. ESCs have the characteristic properties of a stem cell: self-renewal and differentiation. These parent stem cells, ESCs, give rise to progenitor cells, which are intermediate stem cells that lose potency. Progenitor stem cells are committed to differentiating along a particular cell developmental pathway. ESCs will eventually produce endothelial cells (ECs), which create the thin-walled endothelium that lines the inner surface of blood vessels and lymphatic vessels. The lymphatic vessels include things such as arteries and veins. Endothelial cells can be found throughout the whole vascular system and they also play a vital role in the movement of white blood cells
Endothelial progenitor cell 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.
Vascular endothelial growth factor A (VEGF-A) is a protein that in humans is encoded by the VEGFA gene.
The leptomeningeal collateral circulation is a network of small blood vessels in the brain that connects branches of the middle, anterior and posterior cerebral arteries, with variation in its precise anatomy between individuals. During a stroke, leptomeningeal collateral vessels allow limited blood flow when other, larger blood vessels provide inadequate blood supply to a part of the brain.
Angiogenesis is the process of forming new blood vessels from existing blood vessels, formed in vasculogenesis. It is a highly complex process involving extensive interplay between cells, soluble factors, and the extracellular matrix (ECM). Angiogenesis is critical during normal physiological development, but it also occurs in adults during inflammation, wound healing, ischemia, and in pathological conditions such as rheumatoid arthritis, hemangioma, and tumor growth. Proteolysis has been indicated as one of the first and most sustained activities involved in the formation of new blood vessels. Numerous proteases including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase domain (ADAM), a disintegrin and metalloproteinase domain with throbospondin motifs (ADAMTS), and cysteine and serine proteases are involved in angiogenesis. This article focuses on the important and diverse roles that these proteases play in the regulation of angiogenesis.
HP59 is a pathologic angiogenesis capillary endothelial marker protein which has been identified as the receptor for the Group B Streptococcal Toxin molecule known as CM101, the etiologic agent for early-onset versus late-onset Group B Strep.
Vascular remodelling is a process which occurs when an immature heart begins contracting, pushing fluid through the early vasculature. The process typically begins at day 22, and continues to the tenth week of human embryogenesis. This first passage of fluid initiates a signal cascade and cell movement based on physical cues including shear stress and circumferential stress, which is necessary for the remodelling of the vascular network, arterial-venous identity, angiogenesis, and the regulation of genes through mechanotransduction. This embryonic process is necessary for the future stability of the mature vascular network.
Neuroangiogenesis is the coordinated growth of nerves and blood vessels. The nervous and blood vessel systems share guidance cues and cell-surface receptors allowing for this synchronised growth. The term neuroangiogenesis only came into use in 2002 and the process was previously known as neurovascular patterning. The combination of neurogenesis and angiogenesis is an essential part of embryonic development and early life. It is thought to have a role in pathologies such as endometriosis, brain tumors, and Alzheimer's disease.
Tumor-associated endothelial cells or tumor endothelial cells (TECs) refers to cells lining the tumor-associated blood vessels that control the passage of nutrients into surrounding tumor tissue. Across different cancer types, tumor-associated blood vessels have been discovered to differ significantly from normal blood vessels in morphology, gene expression, and functionality in ways that promote cancer progression. There has been notable interest in developing cancer therapeutics that capitalize on these abnormalities of the tumor-associated endothelium to destroy tumors.
Ras-interacting protein 1(Rain), is a protein that in humans is encoded by the RASIP1 gene.
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