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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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.
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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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