Abstract 18683: Satellite Cells are a Major Source of the Receptor for Advanced Glycation End Products in the Ischemic Leg and Play a Role in Collateral Growth
Both coronary artery and peripheral vascular disease are growing health concerns that can lead to impaired blood flow and tissue ischemia, though neovascularization and growth of collateral vessels can help to restore blood flow and preserve tissue function, thus improving outcomes. Collateral formation is a complex process which includes both angiogenesis and arteriogenesis and involves cytokine signaling, inflammatory cells, cell proliferation and migration, and matrix remodeling. One factor that has been associated with negative effects on collateral growth is the receptor for advanced glycation end products (RAGE); however, the cellular source and the mechanism of RAGE regulation in ischemic regions is not fully understood. The goal of this study was to determine if RAGE is increased in the ischemic leg using the hind limb ischemia (HLI) model of collateral growth and to investigate the mechanism regulating its expression using both in vivo and in vitro systems. Following ligation of the femoral artery in the HLI model, RAGE mRNA expression was increased 12.2 ± 3.9 fold in the ischemic versus non-ischemic leg at day 5 (n=6, p=0.007). However, the infusion of PEG-Catalase to decrease hydrogen peroxide significantly blunted the increase (1.4 ± 0.5 versus 12.2 ± 3.9 fold increase (ischemic/non-ischemic) in the PEG-Catalase treated versus control mice, n=6, p=0.0007). These results suggest that RAGE expression is increased by hydrogen peroxide. In situ hybridization revealed that satellite cells are the source of RAGE in the ischemic limb. A primary cell line of satellite cells was established and stimulation with exogenous hydrogen peroxide showed a 2.3 ± 0.3 fold increase in RAGE mRNA expression at 4 hours, as quantified by qRT-PCR. Furthermore, cultured satellite cells also have a 4.0 ± 1.9 fold increase in monocyte chemoattractant protein-1 (MCP-1) at 4 hours and osteopontin was increased 4.5 ± 2.0 fold at 18 hours. Thus, in addition to being a major source of RAGE in the ischemic limb, satellite cells may serve as a novel source of paracrine factors that regulate collateral vessel formation.
Author Disclosures: L.M. Hansen: None. A.N. Lyle: None. G. Joseph: None. D. Weiss: None. W. Taylor: Research Grant; Modest; NIH funding.
- © 2014 by American Heart Association, Inc.