Premium
Temporally‐controlled Cell Labelling Reveals Transdifferentiation of Smooth Muscle Cells during Atherogenesis
Author(s) -
Feil Susanne,
Fehrenbacher Birgit,
Schaller Martin,
Feil Robert
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb573
Subject(s) - transdifferentiation , vascular smooth muscle , biology , microbiology and biotechnology , phenotype , cell type , myocyte , cell , endocrinology , stem cell , smooth muscle , biochemistry , gene
Atherosclerosis and its secondary disorders, heart attack and stroke, are the major causes of death in the western world, but their pathogenesis is poorly understood. One question is how vascular smooth muscle cells (VSMCs) contribute to atherogenesis. In this study, temporally‐controlled Cre/lox‐mediated cell fate mapping was used to investigate the role of VSMCs in atherosclerotic plaque formation in apolipoprotein E‐deficient mice. Prior to development of atherosclerosis, VSMCs were genetically labelled and their fate was followed during disease progression. Our in vivo analyses showed that distinct plaque regions are composed of clonally growing VSMC‐derived cells, which drastically changed their phenotype. These phenotypic changes were further evaluated by expression profiling of cultured VSMCs as an in vitro model of atherogenesis. Both the synthetic/dedifferentiated VSMCs in cell culture and the VSMC‐derived plaque cells in vivo lost typical smooth muscle markers (e.g., SM alpha‐actin) and instead expressed macrophage markers (e.g., Mac‐2 and CD68) and proteins associated with cellular growth and stress. Interestingly, we found that cGMP signalling via cGMP‐dependent protein kinase I might be involved in the development of the VSMC‐derived plaque cells. These findings provide strong in vivo evidence for smooth muscle‐to‐macrophage transdifferentiation and support important roles of cGMP and VSMC plasticity in atherogenesis. Targeting this type of VSMC phenotypic conversion might be a novel strategy for the treatment of atherosclerosis as well as other diseases with a smooth muscle component.