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Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease
Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) ha...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320804/ https://www.ncbi.nlm.nih.gov/pubmed/30544841 http://dx.doi.org/10.3390/ijms19123954 |
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author | Giarretta, Igor Gatto, Ilaria Marcantoni, Margherita Lupi, Giulia Tonello, Diego Gaetani, Eleonora Pitocco, Dario Iezzi, Roberto Truma, Addolorata Porfidia, Angelo Visonà, Adriana Tondi, Paolo Pola, Roberto |
author_facet | Giarretta, Igor Gatto, Ilaria Marcantoni, Margherita Lupi, Giulia Tonello, Diego Gaetani, Eleonora Pitocco, Dario Iezzi, Roberto Truma, Addolorata Porfidia, Angelo Visonà, Adriana Tondi, Paolo Pola, Roberto |
author_sort | Giarretta, Igor |
collection | PubMed |
description | Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs—produced either by endothelial cells, platelets, leukocytes, and erythrocytes—was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs—which was measured in MP-depleted plasma—was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications. |
format | Online Article Text |
id | pubmed-6320804 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63208042019-01-07 Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease Giarretta, Igor Gatto, Ilaria Marcantoni, Margherita Lupi, Giulia Tonello, Diego Gaetani, Eleonora Pitocco, Dario Iezzi, Roberto Truma, Addolorata Porfidia, Angelo Visonà, Adriana Tondi, Paolo Pola, Roberto Int J Mol Sci Article Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs—produced either by endothelial cells, platelets, leukocytes, and erythrocytes—was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs—which was measured in MP-depleted plasma—was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications. MDPI 2018-12-09 /pmc/articles/PMC6320804/ /pubmed/30544841 http://dx.doi.org/10.3390/ijms19123954 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Giarretta, Igor Gatto, Ilaria Marcantoni, Margherita Lupi, Giulia Tonello, Diego Gaetani, Eleonora Pitocco, Dario Iezzi, Roberto Truma, Addolorata Porfidia, Angelo Visonà, Adriana Tondi, Paolo Pola, Roberto Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease |
title | Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease |
title_full | Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease |
title_fullStr | Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease |
title_full_unstemmed | Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease |
title_short | Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease |
title_sort | microparticles carrying sonic hedgehog are increased in humans with peripheral artery disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320804/ https://www.ncbi.nlm.nih.gov/pubmed/30544841 http://dx.doi.org/10.3390/ijms19123954 |
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