Intussusceptive angiogenesis

Type of angiogenesis

For other uses, see Intussusception (disambiguation).

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.[1][2][3] Intussusception occurs in normal development as well as in pathologic conditions involving wound healing,[4] tissue regeneration, inflammation as colitis[5][6] or myocarditis,[7] lung fibrosis,[8] and tumors[9][10] amongst others.

Intussusception was first observed in neonatal rats. In this type of vessel formation, the capillary 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 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 pericytes and myofibroblasts. These cells begin laying collagen fibers into the core to provide an extracellular matrix 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 without a corresponding increase in the number of endothelial cells. 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[11][12] 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.[13]

## Research[edit]

In a small study comparing the lungs of patients who had died from COVID-19 to those that had died from influenza A 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.[14][15]

## References[edit]

1. ^ Djonov, V.; Schmid, M.; Tschanz, S. A.; Burri, P. H. (2000-02-18). "Intussusceptive angiogenesis: its role in embryonic vascular network formation". Circulation Research. 86 (3): 286–292. doi:10.1161/01.res.86.3.286. ISSN 1524-4571. PMID 10679480. S2CID 45113283.
2. ^ Makanya, Andrew N.; Hlushchuk, Ruslan; Djonov, Valentin G. (2009). "Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling". Angiogenesis. 12 (2): 113–123. doi:10.1007/s10456-009-9129-5. ISSN 1573-7209. PMID 19194777. S2CID 8145437.
3. ^ De Spiegelaere, Ward; Casteleyn, Christophe; Van den Broeck, Wim; Plendl, Johanna; Bahramsoltani, Mahtab; Simoens, Paul; Djonov, Valentin; Cornillie, Pieter (2012). "Intussusceptive Angiogenesis: A Biologically Relevant Form of Angiogenesis". Journal of Vascular Research. 49 (5): 390–404. doi:10.1159/000338278. ISSN 1018-1172. PMID 22739226.
4. ^ Erba, Paolo; Ogawa, Rei; Ackermann, Maximilian; Adini, Avner; Miele, Lino F.; Dastouri, Pouya; Helm, Doug; Mentzer, Steven J.; D’Amato, Robert J.; Murphy, George F.; Konerding, Moritz A.; Orgill, Dennis P. (February 2011). "Angiogenesis in Wounds Treated by Microdeformational Wound Therapy". Annals of Surgery. 253 (2): 402–409. doi:10.1097/SLA.0b013e31820563a8. PMC 3403722. PMID 21217515.
5. ^ Konerding, Moritz A.; Turhan, Aslihan; Ravnic, Dino J.; Lin, Miao; Fuchs, Christine; Secomb, Timothy W.; Tsuda, Akira; Mentzer, Steven J. (May 2010). "Inflammation-Induced Intussusceptive Angiogenesis in Murine Colitis". The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology. 293 (5): 849–857. doi:10.1002/ar.21110. PMC 3045768. PMID 20225210.
6. ^ Ackermann, Maximilian; Tsuda, Akira; Secomb, Timothy W.; Mentzer, Steven J.; Konerding, Moritz A. (May 2013). "Intussusceptive remodeling of vascular branch angles in chemically-induced murine colitis". Microvascular Research. 87: 75–82. doi:10.1016/j.mvr.2013.02.002. PMC 3627825. PMID 23485588.
7. ^ Ackermann, Maximilian; Wagner, Willi L.; Rellecke, Philipp; Akhyari, Payam; Boeken, Udo; Reinecke, Petra (21 March 2020). "Parvovirus B19-induced angiogenesis in fulminant myocarditis". European Heart Journal. 41 (12): 1309. doi:10.1093/eurheartj/ehaa092. ISSN 0195-668X. PMID 32101607.
8. ^ Ackermann, Maximilian; Stark, Helge; Neubert, Lavinia; Schubert, Stephanie; Borchert, Paul; Linz, Friedemann; Wagner, Willi L.; Stiller, Wolfram; Wielpütz, Mark; Hoefer, Anne; Haverich, Axel; Mentzer, Steven J.; Shah, Harshit R.; Welte, Tobias; Kuehnel, Mark; Jonigk, Danny (March 2020). "Morphomolecular motifs of pulmonary neoangiogenesis in interstitial lung diseases". European Respiratory Journal. 55 (3): 1900933. doi:10.1183/13993003.00933-2019. PMID 31806721. S2CID 208742259.
9. ^ Ribatti, Domenico; Djonov, Valentin (March 2012). "Intussusceptive microvascular growth in tumors". Cancer Letters. 316 (2): 126–131. doi:10.1016/j.canlet.2011.10.040. PMID 22197620.
10. ^ Ackermann, Maximilian; Morse, Brent A.; Delventhal, Vera; Carvajal, Irvith M.; Konerding, Moritz A. (23 August 2012). "Anti-VEGFR2 and anti-IGF-1R-Adnectins inhibit Ewing's sarcoma A673-xenograft growth and normalize tumor vascular architecture". Angiogenesis. 15 (4): 685–695. doi:10.1007/s10456-012-9294-9. PMID 22914877. S2CID 55783.
11. ^ Nitzsche, Bianca; Rong, Wen Wei; Goede, Andrean; Hoffmann, Björn; Scarpa, Fabio; Kuebler, Wolfgang M.; Secomb, Timothy W.; Pries, Axel R. (February 2022). "Coalescent angiogenesis-evidence for a novel concept of vascular network maturation". Angiogenesis. 25 (1): 35–45. doi:10.1007/s10456-021-09824-3. ISSN 1573-7209. PMC 8669669. PMID 34905124.
12. ^ Pezzella, Francesco; Kerbel, Robert S. (February 2022). "On coalescent angiogenesis and the remarkable flexibility of blood vessels". Angiogenesis. 25 (1): 1–3. doi:10.1007/s10456-021-09825-2. ISSN 1573-7209. PMID 34993716. S2CID 254188870.
13. ^ Dudley AC, Griffioen AW (April 2023). "Pathological angiogenesis: mechanisms and therapeutic strategies". Angiogenesis. 26 (3): 313–347. doi:10.1007/s10456-023-09876-7. PMC 10105163. PMID 37060495.
14. ^ Ackermann, Maximilian; Verleden, Stijn E.; Kuehnel, Mark; Haverich, Axel; Welte, Tobias; Laenger, Florian; Vanstapel, Arno; Werlein, Christopher; Stark, Helge; Tzankov, Alexandar; Li, William W.; Li, Vincent W.; Mentzer, Steven J.; Jonigk, Danny (21 May 2020). "Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19". New England Journal of Medicine. 383 (2): 120–128. doi:10.1056/NEJMoa2015432. PMC 7412750. PMID 32437596.
15. ^ "Injury patterns in COVID-19 lungs". Panta Rhei Study Group. Retrieved 6 July 2020.

* 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, 2003 Oct;314(1):107-17
* Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19 [published online ahead of print, 2020 May 21]. N Engl J Med. 2020;10.1056/NEJMoa2015432. doi:10.1056/NEJMoa2015432
* www.intussusception.org

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Wound healing

* Fibrosis
* Maggot therapy
* Granulation tissue
* Growth factor
* Scar
* Stem cell
* Angiogenesis
* Intussusception
* Vasculogenesis

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