Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats

Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular...

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Main Authors: Jorge Berlanga-Acosta, Maday Fernández-Mayola, Yssel Mendoza-Marí, Ariana García-Ojalvo, Indira Martinez-Jimenez, Nadia Rodriguez-Rodriguez, Raymond J. Playford, Osvaldo Reyes-Acosta, Laura Lopez-Marín, Gerardo Guillén-Nieto
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/23/3/1511
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author Jorge Berlanga-Acosta
Maday Fernández-Mayola
Yssel Mendoza-Marí
Ariana García-Ojalvo
Indira Martinez-Jimenez
Nadia Rodriguez-Rodriguez
Raymond J. Playford
Osvaldo Reyes-Acosta
Laura Lopez-Marín
Gerardo Guillén-Nieto
author_facet Jorge Berlanga-Acosta
Maday Fernández-Mayola
Yssel Mendoza-Marí
Ariana García-Ojalvo
Indira Martinez-Jimenez
Nadia Rodriguez-Rodriguez
Raymond J. Playford
Osvaldo Reyes-Acosta
Laura Lopez-Marín
Gerardo Guillén-Nieto
author_sort Jorge Berlanga-Acosta
collection DOAJ
description Lower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may be transmitted through soluble signaling messengers, transferred from humans to healthy recipient animals, and consequently drive the recapitulation of arterial wall thickening and other vascular pathologies. We examined the effects of the intralesional infiltration for 6 days of arteriosclerotic popliteal artery-derived homogenates (100 µg of protein) into rats’ full-thickness wounds granulation tissue. Animals infiltrated with normal saline solution or healthy brachial arterial tissue homogenate obtained from traumatic amputation served as controls. The significant thickening of arteriolar walls was the constant outcome in two independent experiments for animals receiving arteriosclerotic tissue homogenates. This material induced other vascular morphological changes including an endothelial cell phenotypic reprogramming that mirrored the donor’s vascular histopathology. The immunohistochemical expression pattern of relevant vascular markers appeared to match between the human tissue and the corresponding recipient rats. These changes occurred within days of administration, and with no cross-species limitation. The identification of these “vascular disease drivers” may pave novel research avenues for atherosclerosis pathobiology.
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spelling doaj.art-387d63d6e12f47dda31d3fbc88756d622023-11-23T16:41:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233151110.3390/ijms23031511Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient RatsJorge Berlanga-Acosta0Maday Fernández-Mayola1Yssel Mendoza-Marí2Ariana García-Ojalvo3Indira Martinez-Jimenez4Nadia Rodriguez-Rodriguez5Raymond J. Playford6Osvaldo Reyes-Acosta7Laura Lopez-Marín8Gerardo Guillén-Nieto9Tissue Repair, Wound Healing and Cytoprotection Research Group, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Ave. 31 S/N. e/158 and 190, Cubanacán, Playa, Havana 10600, CubaTissue Repair, Wound Healing and Cytoprotection Research Group, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Ave. 31 S/N. e/158 and 190, Cubanacán, Playa, Havana 10600, CubaTissue Repair, Wound Healing and Cytoprotection Research Group, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Ave. 31 S/N. e/158 and 190, Cubanacán, Playa, Havana 10600, CubaTissue Repair, Wound Healing and Cytoprotection Research Group, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Ave. 31 S/N. e/158 and 190, Cubanacán, Playa, Havana 10600, CubaTissue Repair, Wound Healing and Cytoprotection Research Group, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Ave. 31 S/N. e/158 and 190, Cubanacán, Playa, Havana 10600, CubaTissue Repair, Wound Healing and Cytoprotection Research Group, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Ave. 31 S/N. e/158 and 190, Cubanacán, Playa, Havana 10600, CubaSchool of Biomedical Sciences, University of West London, St Marys Rd, Ealing, London W5 5RF, UKTissue Repair, Wound Healing and Cytoprotection Research Group, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Ave. 31 S/N. e/158 and 190, Cubanacán, Playa, Havana 10600, CubaDepartment of Pathology, Institute for Arteriosclerosis Research, Institute of Nephrology “Dr. Abelardo Buch”, Calle 26 y Línea del Ferrocarril, Vedado, Havana 10400, CubaTissue Repair, Wound Healing and Cytoprotection Research Group, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Ave. 31 S/N. e/158 and 190, Cubanacán, Playa, Havana 10600, CubaLower-extremity arterial disease is a major health problem with increasing prevalence, often leading to non-traumatic amputation, disability and mortality. The molecular mechanisms underpinning abnormal vascular wall remodeling are not fully understood. We hypothesized on the existence of a vascular tissue memory that may be transmitted through soluble signaling messengers, transferred from humans to healthy recipient animals, and consequently drive the recapitulation of arterial wall thickening and other vascular pathologies. We examined the effects of the intralesional infiltration for 6 days of arteriosclerotic popliteal artery-derived homogenates (100 µg of protein) into rats’ full-thickness wounds granulation tissue. Animals infiltrated with normal saline solution or healthy brachial arterial tissue homogenate obtained from traumatic amputation served as controls. The significant thickening of arteriolar walls was the constant outcome in two independent experiments for animals receiving arteriosclerotic tissue homogenates. This material induced other vascular morphological changes including an endothelial cell phenotypic reprogramming that mirrored the donor’s vascular histopathology. The immunohistochemical expression pattern of relevant vascular markers appeared to match between the human tissue and the corresponding recipient rats. These changes occurred within days of administration, and with no cross-species limitation. The identification of these “vascular disease drivers” may pave novel research avenues for atherosclerosis pathobiology.https://www.mdpi.com/1422-0067/23/3/1511critical limb ischemiaarterial diseasearteriosclerosisangiopathy
spellingShingle Jorge Berlanga-Acosta
Maday Fernández-Mayola
Yssel Mendoza-Marí
Ariana García-Ojalvo
Indira Martinez-Jimenez
Nadia Rodriguez-Rodriguez
Raymond J. Playford
Osvaldo Reyes-Acosta
Laura Lopez-Marín
Gerardo Guillén-Nieto
Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats
International Journal of Molecular Sciences
critical limb ischemia
arterial disease
arteriosclerosis
angiopathy
title Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats
title_full Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats
title_fullStr Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats
title_full_unstemmed Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats
title_short Intralesional Infiltrations of Arteriosclerotic Tissue Cells-Free Filtrate Reproduce Vascular Pathology in Healthy Recipient Rats
title_sort intralesional infiltrations of arteriosclerotic tissue cells free filtrate reproduce vascular pathology in healthy recipient rats
topic critical limb ischemia
arterial disease
arteriosclerosis
angiopathy
url https://www.mdpi.com/1422-0067/23/3/1511
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