Intussusceptive angiogenesis

Short description: Type of 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.[1] Intussusception occurs in normal development as well as in pathologic conditions involving wound healing,[2] tissue regeneration, inflammation as colitis[3][4] or myocarditis,[5] lung fibrosis,[6] and tumors[7][8] 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.

## Research

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.[9][10]

## References

1. ↑ 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" (in english). Journal of Vascular Research 49 (5): 390–404. doi:10.1159/000338278. ISSN 1018-1172. PMID 22739226.
2. ↑ Erba, Paolo; Ogawa, Rei; Ackermann, Maximilian; Adini, Avner; Miele, Lino F.; Dastouri, Pouya; Helm, Doug; Mentzer, Steven J. et al. (February 2011). "Angiogenesis in Wounds Treated by Microdeformational Wound Therapy". Annals of Surgery 253 (2): 402–409. doi:10.1097/SLA.0b013e31820563a8. PMID 21217515.
3. ↑ 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. PMID 20225210.
4. ↑ 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. PMID 23485588.
5. ↑ Ackermann, Maximilian; Wagner, Willi L.; Rellecke, Philipp; Akhyari, Payam; Boeken, Udo; Reinecke, Petra (21 March 2020). "Parvovirus B19-induced angiogenesis in fulminant myocarditis" (in en). European Heart Journal 41 (12): 1309. doi:10.1093/eurheartj/ehaa092. ISSN 0195-668X. PMID 32101607.
6. ↑ Ackermann, Maximilian; Stark, Helge; Neubert, Lavinia; Schubert, Stephanie; Borchert, Paul; Linz, Friedemann; Wagner, Willi L.; Stiller, Wolfram et al. (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.
7. ↑ 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.
8. ↑ 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.
9. ↑ Ackermann, Maximilian; Verleden, Stijn E.; Kuehnel, Mark; Haverich, Axel; Welte, Tobias; Laenger, Florian; Vanstapel, Arno; Werlein, Christopher et al. (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. PMID 32437596.
10. ↑ "Injury patterns in COVID-19 lungs". https://www.intussusception.org/covid19.

* 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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