LAUSR

Objectives: Diabetic patients suffer an increased risk of restenosis and late stent thrombosis after angioplasty, complications that are related to a defective re-endothelialization. Dipeptidyl peptidase-4 inhibitors have been suggested to exert direct effect on endothelial and smooth muscle cells (SMCs). Therefore, the objective was to study whether the dipeptidyl peptidase-4 inhibitor linagliptin could influence vascular repair and accelerate re-endothelialization after arterial injury in healthy and diabetic animals. Methods: Diabetic Goto-Kakizaki and healthy Wistar rats were subjected to arterial injury and treated with linagliptin or vehicle. Vessel wall healing was monitored noninvasively using ultrasound imaging and upon sacrifice with Evans blue staining and immunohistochemistry. The effect of linagliptin on SMCs was also studied in vitro. Results: We observed a delay in the healing response in the diabetic animals compared with the Wistar controls. Goto-Kakizaki rats had more pronounced intimal hyperplasia, which affected the lumen diameter. We found that linagliptin reduced the proliferation and dedifferentiation of SMCs in vitro and modulated the inflammatory response in the SMCs after arterial injury in vivo. However, these effects of linagliptin did not affect the neointima formation or the re-endothelialization under normal and diabetic conditions. Conclusions: Although linagliptin did not influence vessel wall healing, it appears to possess a desirable antiproliferative influence on SMCs in vitro and an anti-inflammatory effect in vivo. These pharmacologic properties might carry a potential significance for favorable outcome after vascular interventions in diabetic patients.