Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease

Igor Giarretta
ORCID logo ,
Ilaria Gatto
,
Margherita Marcantoni
,
Giulia Lupi
,
Diego Tonello
,
Eleonora Gaetani
,
Dario Pitocco
,
Roberto Iezzi
,
Ada Truma
,
Angelo Porfidia
,
Adriana Visonà
,
Paolo Tondi
,
Roberto Pola
* ORCID logo
These authors contributed equally to this work.
Version 1 : Received: 1 August 2018 / Approved: 2 August 2018 / Online: 2 August 2018 (05:20:58 CEST)

How to cite: Giarretta, I.; Gatto, I.; Marcantoni, M.; Lupi, G.; Tonello, D.; Gaetani, E.; Pitocco, D.; Iezzi, R.; Truma, A.; Porfidia, A.; Visonà, A.; Tondi, P.; Pola, R. Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease. Preprints 2018, 2018080033. https://doi.org/10.20944/preprints201808.0033.v1 Giarretta, I.; Gatto, I.; Marcantoni, M.; Lupi, G.; Tonello, D.; Gaetani, E.; Pitocco, D.; Iezzi, R.; Truma, A.; Porfidia, A.; Visonà, A.; Tondi, P.; Pola, R. Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease. Preprints 2018, 2018080033. https://doi.org/10.20944/preprints201808.0033.v1

Abstract

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. In this study, the plasma number of Shh+ MPs in patients with peripheral artery disease (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. Interestingly, the concentration of Shh protein unbound to MPs – which was measured in MP-depleted plasma – was not different between subjects with PAD and 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 insights on the mechanisms through which the Shh signaling is reactivated during ischemia in humans, with potentially important fundamental and clinical implications.

Keywords

sonic hedgehog; microparticles; peripheral artery disease

Subject

Biology and Life Sciences, Anatomy and Physiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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