OBJECTIVES - Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. APPROACH AND RESULTS - We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R). Endothelial regeneration after arterial injury was accelerated in IGF1R mice. Although the yield of angiogenic progenitor cells was lower in IGF1R mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R bone marrow-derived CD117 cells into wild-type mice. IGF1R cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. CONCLUSIONS - Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117 cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury.
|Number of pages||8|
|Journal||Arteriosclerosis, Thrombosis, and Vascular Biology|
|Early online date||10 Jul 2014|
|Publication status||Published - 1 Sep 2014|
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- Department of Optometry and Vision Sciences - Lecturer in Physiology (with teaching contributing to Optometry)
- School of Applied Sciences
- Cellular and Molecular Models of Disease Centre - Member
- Centre for Vision across the Life Span - Member