Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding †

The historical development of discoveries and conceptual frames for understanding the hemorrhagic activity induced by viperid snake venoms and by hemorrhagic metalloproteinases (SVMPs) present in these venoms is reviewed. Histological and ultrastructural tools allowed the identification of the capil...

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Main Authors:	Gutiérrez, José María, Escalante, Teresa, Rucavado, Alexandra, Herrera, Cristina
Format:	Online
Language:	English
Published:	MDPI 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848620/

id	pubmed-4848620
recordtype	oai_dc
spelling	pubmed-48486202016-05-04 Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding † Gutiérrez, José María Escalante, Teresa Rucavado, Alexandra Herrera, Cristina Review The historical development of discoveries and conceptual frames for understanding the hemorrhagic activity induced by viperid snake venoms and by hemorrhagic metalloproteinases (SVMPs) present in these venoms is reviewed. Histological and ultrastructural tools allowed the identification of the capillary network as the main site of action of SVMPs. After years of debate, biochemical developments demonstrated that all hemorrhagic toxins in viperid venoms are zinc-dependent metalloproteinases. Hemorrhagic SVMPs act by initially hydrolyzing key substrates at the basement membrane (BM) of capillaries. This degradation results in the weakening of the mechanical stability of the capillary wall, which becomes distended owing of the action of the hemodynamic biophysical forces operating in the circulation. As a consequence, the capillary wall is disrupted and extravasation occurs. SVMPs do not induce rapid toxicity to endothelial cells, and the pathological effects described in these cells in vivo result from the mechanical action of these hemodynamic forces. Experimental evidence suggests that degradation of type IV collagen, and perhaps also perlecan, is the key event in the onset of microvessel damage. It is necessary to study this phenomenon from a holistic, systemic perspective in which the action of other venom components is also taken into consideration. MDPI 2016-03-26 /pmc/articles/PMC4848620/ /pubmed/27023608 http://dx.doi.org/10.3390/toxins8040093 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gutiérrez, José María Escalante, Teresa Rucavado, Alexandra Herrera, Cristina
spellingShingle	Gutiérrez, José María Escalante, Teresa Rucavado, Alexandra Herrera, Cristina Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding †
author_facet	Gutiérrez, José María Escalante, Teresa Rucavado, Alexandra Herrera, Cristina
author_sort	Gutiérrez, José María
title	Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding †
title_short	Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding †
title_full	Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding †
title_fullStr	Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding †
title_full_unstemmed	Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding †
title_sort	hemorrhage caused by snake venom metalloproteinases: a journey of discovery and understanding †
description	The historical development of discoveries and conceptual frames for understanding the hemorrhagic activity induced by viperid snake venoms and by hemorrhagic metalloproteinases (SVMPs) present in these venoms is reviewed. Histological and ultrastructural tools allowed the identification of the capillary network as the main site of action of SVMPs. After years of debate, biochemical developments demonstrated that all hemorrhagic toxins in viperid venoms are zinc-dependent metalloproteinases. Hemorrhagic SVMPs act by initially hydrolyzing key substrates at the basement membrane (BM) of capillaries. This degradation results in the weakening of the mechanical stability of the capillary wall, which becomes distended owing of the action of the hemodynamic biophysical forces operating in the circulation. As a consequence, the capillary wall is disrupted and extravasation occurs. SVMPs do not induce rapid toxicity to endothelial cells, and the pathological effects described in these cells in vivo result from the mechanical action of these hemodynamic forces. Experimental evidence suggests that degradation of type IV collagen, and perhaps also perlecan, is the key event in the onset of microvessel damage. It is necessary to study this phenomenon from a holistic, systemic perspective in which the action of other venom components is also taken into consideration.
publisher	MDPI
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848620/
_version_	1613572320112148480

Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding †

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