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Article

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

by
Igor Giarretta
1,†,
Ilaria Gatto
1,†,
Margherita Marcantoni
1,
Giulia Lupi
1,
Diego Tonello
2,
Eleonora Gaetani
1,
Dario Pitocco
3,
Roberto Iezzi
4,
Addolorata Truma
1,
Angelo Porfidia
1,
Adriana Visonà
2,
Paolo Tondi
1 and
Roberto Pola
1,*
1
Department of Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
2
Unit of Angiology, S. Giacomo Hospital, 31033 Castelfranco Veneto, Italy
3
Diabetology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
4
Department of Radiological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(12), 3954; https://doi.org/10.3390/ijms19123954
Submission received: 10 November 2018 / Revised: 2 December 2018 / Accepted: 5 December 2018 / Published: 9 December 2018
(This article belongs to the Special Issue Hedgehog Signaling)
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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. 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.
Keywords: sonic hedgehog; microparticles; peripheral artery disease sonic hedgehog; microparticles; peripheral artery disease

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MDPI and ACS Style

Giarretta, I.; Gatto, I.; Marcantoni, M.; Lupi, G.; Tonello, D.; Gaetani, E.; Pitocco, D.; Iezzi, R.; Truma, A.; Porfidia, A.; et al. Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease. Int. J. Mol. Sci. 2018, 19, 3954. https://doi.org/10.3390/ijms19123954

AMA Style

Giarretta I, Gatto I, Marcantoni M, Lupi G, Tonello D, Gaetani E, Pitocco D, Iezzi R, Truma A, Porfidia A, et al. Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease. International Journal of Molecular Sciences. 2018; 19(12):3954. https://doi.org/10.3390/ijms19123954

Chicago/Turabian Style

Giarretta, Igor, Ilaria Gatto, Margherita Marcantoni, Giulia Lupi, Diego Tonello, Eleonora Gaetani, Dario Pitocco, Roberto Iezzi, Addolorata Truma, Angelo Porfidia, and et al. 2018. "Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease" International Journal of Molecular Sciences 19, no. 12: 3954. https://doi.org/10.3390/ijms19123954

APA Style

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. (2018). Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease. International Journal of Molecular Sciences, 19(12), 3954. https://doi.org/10.3390/ijms19123954

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