Intussusceptive angiogenesis also known as splitting angiogenesis, is a type of

angiogenesis 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 ...

, the process whereby a new

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

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. Intussusception was first observed in neonatal rats. In this type of vessel formation, the

capillary 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 (the inn ...

wall extends into the lumen to split a single vessel in two. There are four phases of intussusceptive angiogenesis. First, the two opposing capillary walls establish a zone of contact. Second, the

endothelial cell The endothelium (: endothelia) 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 th ...

junctions are reorganized and the vessel bilayer is perforated to allow growth factors and cells to penetrate into the lumen. Third, a core is formed between the two new vessels at the zone of contact that is filled with

pericyte Pericytes (formerly called Rouget cells) 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 c ...

s and

myofibroblasts A myofibroblast is a cell phenotype that was first described as being in a state between a fibroblast and a smooth muscle cell. Structure Myofibroblasts are contractile web-like fusiform cells that are identifiable by their expression of α-s ...

. These cells begin laying

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

fibers into the core to provide an

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

for growth of the vessel lumen. Finally, the core is fleshed out with no alterations to the basic structure. Intussusception is important because it is a reorganization of existing cells. It allows a vast increase in the number of

capillaries 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 (the in ...

without a corresponding increase in the number of

s. This is especially important in embryonic development as there are not enough resources to create a rich microvasculature with new cells every time a new vessel develops. A process called

coalescent angiogenesis 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 acti ...

is considered the opposite of intussusceptive angiogenesis. During coalescent angiogenesis capillaries fuse and form larger vessels to increase blood flow and circulation. Several other modes of angiogenesis have been described, such as sprouting angiogenesis, vessel co-option and vessel elongation.

Research

In a small study comparing the lungs of patients who had died from

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...

to those that had died from

influenza A ''Influenza A virus'' (''Alphainfluenzavirus influenzae'') or IAV is the only species of the genus ''Alphainfluenzavirus'' of the virus family '' Orthomyxoviridae''. It is a pathogen with strains that infect birds and some mammals, as well as c ...

pneumonia (H1N1) to uninfected controls during autopsy; there was a significantly greater density of intussusceptive angiogenic features in the lungs of patients who had died from Covid-19 as compared to influenza A and the control group. The degree of intussusceptive angiogenic features in the lungs from the Covid-19 patients were also found to be greater as the length of hospitalization increased (which was not seen in the influenza or control groups). This suggests that increased or enhanced intussusceptive angiogenesis is seen in Covid-19 and may play a role in pathogenesis.

References

*''Mentzer SJ, Konerding MA. Intussusceptive angiogenesis: Expansion and remodeling of microvascular networks''. Angiogenesis 2014;17:499-509. *''Vascular remodeling by intussusceptive angiogenesis'', Djonov V, Baum O, Burri PH.,

Cell and Tissue Research ''Cell and Tissue Research'' presents regular articles and reviews in the areas of molecular, cell, stem cell biology and tissue engineering. In particular, the journal provides a forum for publishing data that analyze the supracellular, integrati ...

, 2003 Oct;314(1):107-17 * *
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