Increased skin inflammation and blood vessel density in human and experimental diabetes

Abstract

Systemic inflammation is associated with impaired wound healing in diabetes mellitus (DM) patients. Using immunohistochemistry techniques, the authors investigated changes in skin inflammation and skin blood vessels in human and experimental diabetes. Comparing to the non-DM human subjects, the total number of inflammatory cells per biopsy and the number of inflammatory cells around blood vessels, a strong indication of inflammation, were higher in DM subjects irrespective of their risk for developing diabetic foot ulcer. Inflammatory cell infiltration was robustly increased in all DM animal models compared with their non-DM controls. The number and density of blood vessels and CD31 positive proliferating endothelial cells around preexisting skin vessels was also higher in the DM patients. However, there were no differences in the skin blood flow between the non-DM and DM subjects. The number of skin blood vessels was also increased in the DM animals; however, these differences were less obvious than the ones observed for inflammatory cells. We conclude that skin inflammation and skin blood vessel density is increased in diabetic human subjects and in rodent and rabbit models of diabetes.

Figure 1

Fold change in the skin inflammatory cells comparing non-diabetic (non-DM) and diabetic (DM) within respective species. Skin inflammatory cells were increased in DM patients with low or high risk for foot problems when compared to non-DM subjects. Similar results were observed in DM rabbits, rats and mice when compared to their non-DM counterparts. Data are presented as mean ± SE.

Figure 2

Images a–f: Representative images of H&E staining in non-DM and DM rabbit ear skin (a and b respectively), non-DM and DM rat skin (c and d) and non-DM and DM mouse skin (e and f). Black arrows indicate round inflammatory cells while green arrows indicate blood vessels. The number of infiltrating inflammatory cells were increased in all diabetic animal models when compared to non-diabetic animals (p<0.05) as well as the number of blood vessels (p<0.05). Images g, f: Representative images of H&E and CD31 staining in the same mouse skin biopsy. H&E staining (g) identified fully formed (mature) skin blood vessels. CD31 staining (h) confirmed that the identified structures in the H&E stained biopsy were blood vessels (green arrows) while it also identified additional endothelial cells that represent newly regenerating blood vessels (red arrows).