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8 HEDGEHOG responsive stem cell ANTIGEN-1/S100β resident vascular stem cells contribute to neointimal formation
  1. Emma Fitzpatrick1,
  2. Weimin Liu2,
  3. Maryam Alshamrani1,
  4. Jay-Christian Helt2,
  5. Roya Hakimjavadi1,
  6. Susan Harman1,
  7. Abidemi Olayinka1,
  8. Denise Burtenshaw1,
  9. Eoin Corcoran1,
  10. Mariana Di Luca1,
  11. Catriona Lally3,
  12. Eileen M Redmond2,
  13. Paul A Cahill1
  1. 1Vascular Biology and Therapeutics Laboratory, School of Biotechnology Faculty of Science and Health, Dublin City University, Dublin 9, Ireland
  2. 2Trinity College Dublin, Trinity Centre For Bioengineering, Trinity Biomedical Sciences Institute, Dublin Ireland
  3. 3Department of Surgery, University of Rochester Medical Centre, Rochester, NY, USA

Abstract

Intimal medial thickening (IMT) and vascular remodelling are hallmarks of arteriosclerotic disease. The origin of neointimal cells and the signalling molecules that direct their fate and function is controversial. Here, we demonstrate that Hedgehog (Hh) responsive S100β+/Sca1+ perivascular stem cells substantially contribute to IMT within carotid arteries of transgenic mice following ligation-induced injury in vivo. Genetic lineage tracing analysis using S100β-eGFP/Cre/ERT2 transgenic mice to mark resident vascular stem cells before injury demonstrated that Hh responsive S100β+/Sca1+ cells substantially contribute to IMT, an effect significantly attenuated following treatment with the Hh smoothened inhibitor, cylopamine. In vitro, recombinant SHh (rSHh) treatment of multipotent S100β+/Sca1+ resident stem cells increased target gene Gli expression, decreased telomerase activity, and promoted myogenic differentiation and cell growth; effects significantly attenuated following Hh inhibition. These findings suggest that perivascular S100β+/Sca1+ stem cells are a major source of neointimal cells contributing to IMT and suggest that this cohort may be a relevant therapeutic target to prevent arteriosclerosis.

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