Microparticles carrying sonic hedgehog are increased in humans with peripheral artery disease

Igor Giarretta, Ilaria Gatto, Margherita Marcantoni, Giulia Lupi, Diego Tonello, Eleonora Gaetani, Dario Pitocco, Roberto Iezzi, Addolorata Truma, Angelo Porfidia, Adriana Visonà, Paolo Tondi, Roberto Pola

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number3954
JournalInternational Journal of Molecular Sciences
Issue number12
Publication statusPublished - Dec 1 2018


  • Microparticles
  • Peripheral artery disease
  • Sonic hedgehog

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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