Preexisting smooth muscle cells contribute to neointimal cell repopulation at an incidence varying widely among individual lesions

Pu Yang, Michael S. Hong, Chunhua Fu, Bradley M. Schmit, Yunchao Su, Scott A. Berceli, Zhihua Jiang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background With the diverse origin of neointimal cells, previous studies have documented differences of neointimal cell lineage composition across models, but the animal-to-animal difference has not attracted much attention, although the cellular heterogeneity may impact neointimal growth and its response to therapeutic interventions. Methods R26R+;Myh11-CreER+, and R26R+;Scl-CreER+ mice were used to attach LacZ tags to the preexisting smooth muscle cells (SMCs) and endothelial cells (ECs), respectively. Neointimal lesions were created via complete ligation of the common carotid artery (CCA) and transluminal injury to the femoral artery (FA). Results LacZ-tagged SMCs were physically relocated from media to neointima and changed to a dedifferentiated phenotype in both CCA and FA lesions. The content of SMCs in the neointimal tissue, however, varied widely among specimens, ranging from 5 to 70% and 0 to 85%, with an average at low levels of 27% and 29% in CCA (n = 15) and FA (n = 15) lesions, respectively. Bone marrow cells, although able to home to the injured arteries, did not differentiate fully into SMCs after either type of injury. Preexisting ECs were located in the subendothelial region and produced mesenchymal marker α-actin, indicating endothelial-mesenchymal transition (EndoMT); however, EC-derived cells represented only 7% and 3% of the total neointimal cell pool of CCA (n = 7) and FA (n = 7) lesions, respectively. ECs located on the luminal surface exhibited little evidence of EndoMT. Conclusion Neointimal hyperplasia proceeds with a wide range of variation in its cellular composition between individual lesions. Relative to ECs, SMCs are major contributors to the lesion-to-lesion heterogeneity in neointimal cell lineage composition.

Original languageEnglish (US)
Pages (from-to)602-612
Number of pages11
JournalSurgery (United States)
Volume159
Issue number2
DOIs
StatePublished - Feb 1 2016

ASJC Scopus subject areas

  • Surgery

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