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. Author manuscript; available in PMC: 2013 Nov 1.
Published in final edited form as: Vascul Pharmacol. 2012 Jun 29;57(5-6):160–167. doi: 10.1016/j.vph.2012.06.004

Figure 3. Soluble RAGE – high vs. low & “good” or “bad?”.

Figure 3

To date, quite a number of human subject studies on sRAGE (total sRAGE or esRAGE) have been reported. Intriguingly, some of these studies suggest that “high” sRAGE may be maladaptive and others show that “low” levels of RAGE are most foreboding for diabetes. What may account for these differences in sRAGE values? We suggest that perhaps in early diabetes, without complications, that levels of sRAGEs are higher than controls without diabetes. Perhaps shedding of the increased expression of cell surface RAGE is a protective mechanism to decoy and trap the accumulating deleterious ligands, such as AGEs, S100/calgranulins, HMGB1 and mac-1. However, in late stages of the disease when quite advanced tissue damage has occurred, lower levels of sRAGEs may be associated with complications. At this stage, perhaps mechanisms that endogenously release the sRAGEs are impaired, and/or that the increased ligand burden consumes all available sRAGEs. Prospective, multi-time point studies, assessing both total sRAGE and esRAGE, are required to sort out the meaning of sRAGEs – are they solely biomarkers or in endogenous antagonists of ligand-RAGE damage?