Aims: Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show increased levels of C-peptide and our group demonstrated C-peptide deposition in human atherosclerotic lesions. Further in-vitro data showed proinflammatory effects of C-peptide in vascular cells. Nothing is known about C-peptides’ vascular effects in animal models, therefore the present study examined C-peptides’ role in atherogenesis.
Methods and Results: We examined the effect of subcutaneously C-peptide administration on atherosclerotic lesion formation in ApoE-deficient mice, which were maintained on a cholesterol diet. Mice were treated for 12 weeks with C-peptide vs. placebo and then pathological analyses were performed. We found a significant increase in C-peptide deposition in atherosclerotic plaques and an induction in macrophage-positive area in the aortic arch. Furthermore the content of smooth muscle cells was increased, and lipid deposition measured by oil-red-O staining was induced in the aortic arch of C-peptide treated mice. A similar trend was observed in the whole aorta, but this effect reached not significance.
Conclusions: Our results demonstrate that C-peptide deposits in atherosclerotic lesions and perpetuates the inflammatory process. These data support the hypothesis of C-peptide’s active role in atherogenesis, especially in patients with diabetes and insulin resistance
