Abstract 81: Novel Adult Endothelial Hierarchy Defined by Endovascular Progenitor Reexpression of SOX18
Introduction: During adult life, formation of new blood vessels in response to insults or physiological signals is thought almost exclusively to result from the sprouting and extension of existing vessels defined as angiogenesis. An alternate proposal for de novo vascularization relates to endothelial progenitors and their ability to assemble the intimal layers of mature vessels. However, the cell lineage and possible hierarchy of such precursors remains controversial. We here aimed to define endothelial progenitors in vivo in situations of neo-vessel formation in adult mice.
Methods and Results: Based on protein expression levels of markers CD31 and VEGFR2 using flow cytometry, three populations of endothelial cells could be identified among VECAD+CD34+CD45- cells in a variety of angiogenic situations such as wound healing, tumours, placental development, or in subcutaneous Matrigel plugs. Lineage tracing based on sox18 re-expression using a sox18CreER/Rosa-YFP reporter strategy demonstrated that the CD31loVEGFR2- endothelial population was indeed an endovascular progenitor (EVP) of an intermediate CD31intVEGFR2- transit amplifying and a definitive differentiated CD31hiVEGFR2hi population. Loss of SOX18, in a dominant-negative mouse model, did not affect levels of EVP populations in vivo, but depleted both the intermediate and definitive populations. Only the sorted CD31loVEGFR2- as opposed to the other two endothelial populations could form colonies in vitro and engraft in vivo in a Matrigel plug assay.
Conclusions: These results define and characterize an in vivo endothelial hierarchy and suggest a prominent role for vessel resident EVP populations in situations of neo-vessel formation. This data opens the medium for new perspectives in modulating blood vessel formation.
Author Disclosures: J. Patel: None. E.J. Seppanen: None. M.P. Rodero: None. E. Roy: None. N.M. Fisk: None. M.C. Yoder: None. M. Francois: None. K. Khosrotehrani: None.
- © 2014 by American Heart Association, Inc.