Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis

S Feil, B Fehrenbacher, R Lukowski… - Circulation …, 2014 - Am Heart Assoc
S Feil, B Fehrenbacher, R Lukowski, F Essmann, K Schulze-Osthoff, M Schaller, R Feil
Circulation research, 2014Am Heart Assoc
Rationale: Atherosclerosis is a widespread and devastating disease, but the origins of cells
within atherosclerotic plaques are not well defined. Objective: To investigate the specific
contribution of vascular smooth muscle cells (SMCs) to atherosclerotic plaque formation by
genetic inducible fate mapping in mice. Methods and Results: Vascular SMCs were
genetically pulse-labeled using the tamoxifen-dependent Cre recombinase, CreERT2,
expressed from the endogenous SM22α locus combined with Cre-activatable reporter …
Rationale:
Atherosclerosis is a widespread and devastating disease, but the origins of cells within atherosclerotic plaques are not well defined.
Objective:
To investigate the specific contribution of vascular smooth muscle cells (SMCs) to atherosclerotic plaque formation by genetic inducible fate mapping in mice.
Methods and Results:
Vascular SMCs were genetically pulse-labeled using the tamoxifen-dependent Cre recombinase, CreERT2, expressed from the endogenous SM22α locus combined with Cre-activatable reporter genes that were integrated into the ROSA26 locus. Mature SMCs in the arterial media were labeled by tamoxifen treatment of young apolipoprotein E–deficient mice before the development of atherosclerosis and then their fate was monitored in older atherosclerotic animals. We found that medial SMCs can undergo clonal expansion and convert to macrophage-like cells that have lost classic SMC marker expression and make up a major component of advanced atherosclerotic lesions.
Conclusions:
This study provides strong in vivo evidence for smooth muscle-to-macrophage transdifferentiation and supports an important role of SMC plasticity in atherogenesis. Targeting this type of SMC phenotypic conversion might be a novel strategy for the treatment of atherosclerosis, as well as other diseases with a smooth muscle component.
Am Heart Assoc