Background
Accelerated cardiovascular disease in patients with type I diabetes (TID) is a well-described condition and serious clinical obstacle. At present, the notion that early atherogenesis is largely dependent on sustained hyperglycemia remains in question. We hypothesize that an alteration in T lymphocyte homeostasis may result in early vascular inflammation, which might amplify subsequent blood vessel injury in euglycemia.
Conclusions
These observations suggest that autoimmunity, in the setting of impending hyperglycemia, may contribute to accelerated vascular inflammation and subsequent pathology.
Methods
A murine model of carotid arterial ligation was employed to induce neointimal hyperplasia (NIH) in C57/Bl6 (non-autoimmune) and non-obese diabetic (NOD) mice. Additionally, adoptive transfer of NOD splenocytes into immunodeficient NOD mice (NOD.scid) was undertaken to evaluate the influence of restored autoimmunity on NIH development.
Results
Interestingly, compared with C57/Bl6 mice, the NOD demonstrate a significant increase in neointimal area. Conversely, the NOD.scid mice (immunodeficient control) reveal almost no evidence of vascular injury. While evidence of early vascular inflammation can be detected in the injured NOD vasculature, uninjured contralateral vessels and those of the NOD.scid have minimal T cell infiltration. Following reconstitution of autoimmune responses via NOD splenocyte adoptive transfer, accelerated vascular pathology is restored. Conclusions: These observations suggest that autoimmunity, in the setting of impending hyperglycemia, may contribute to accelerated vascular inflammation and subsequent pathology.