Abstract 29: Fate-Tracing Demonstrates that Medial SMCs, but Not Mature ECs, Contribute to Neointimal Cell Population in Injured Arteries

It has been proposed that various groups of cells, such as medial SMCs (mSMCs), bone marrow progenitors, and mature ECs (mECs) hold the potential to become neointimal SMCs via phenotypic switching, differentiation, or endothelial-mesenchymal-transition (EMT). However, no definitive evidence has been provided to support these claims, which renders the in vivo significance of these events in question. Using an inducible Cre-loxP system, where the production of a reporter (e.g. β-gal) is driven by a highly definitive marker gene for mSMCs (e.g. SMC myosin heavy chain, SMMHC) or mECs (e.g. stem cell leukemia, SCL), we traced the fate of these cells during neointimal hyperplasia (NIH) in ligated common carotid and wire-injured femoral arteries. Tamoxifen induction resulted in a homogeneous labeling of mSMCs of the unmanipulated arteries of R26R;SMMHC-CreERtm mice. Following arterial injury, SMCs that were initially located in the medial layer presented in neointimal lesions; however, the fraction of these cell...