Original ArticleEffects of Linagliptin on Vessel Wall Healing in the Rat Model of Arterial Injury Under Normal and Diabetic ConditionsEriksson, Linnea PhD*; Röhl, Samuel MD*; Saxelin, Robert MD*; Lengquist, Mariette BSc*; Kronqvist, Malin BSc*; Caidahl, Kenneth MD†; Östenson, Claes-Göran MD†; Razuvaev, Anton MD, PhD*Author Information *Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Solna, Sweden; and †Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden. Reprints: Anton Razuvaev, MD, PhD, Department of Molecular Medicine and Surgery, Karolinska University Hospital, CMM L8:03, Karolinska Institutet, 171 76 Stockholm, Sweden (e-mail: [email protected]). Supported by Boehringer Ingelheim GmbH; Swedish Heart-Lung foundation (grant number 20150282, 20140350); The Swedish Research Council (2014-2326); and The Swedish Diabetes Foundation (DIA2015-033). It was supported in part by Boehringer Ingelheim GmbH; however, they had no involvement in the study design; collection, analysis, and interpretation of data; writing of the report; or in the decision to submit the article for publication. The authors report no conflicts of interest. Journal of Cardiovascular Pharmacology: February 2017 - Volume 69 - Issue 2 - p 101-109 doi: 10.1097/FJC.0000000000000447 Buy Metrics Abstract Diabetic patients suffer an increased risk of restenosis and late stent thrombosis after angioplasty, complications which are related to a defective reendothelialization. Dipeptidyl peptidase-4 inhibitors have been suggested to exert a direct effect on endothelial and smooth muscle cells (SMCs). Therefore, the objective was to study if the dipeptidyl peptidase-4 inhibitor linagliptin could influence vascular repair and accelerate reendothelialization after arterial injury in healthy and diabetic animals. 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, and on sacrifice, with Evans blue staining and immunohistochemistry. The effect of linagliptin on SMCs was also studied in vitro. 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 reendothelialization under normal and diabetic conditions. Although linagliptin did not influence vessel wall healing, it seems to possess a desirable antiproliferative influence on SMCs in vitro and an antiinflammatory effect in vivo. These pharmacological properties might carry a potential significance for favorable outcome after vascular interventions in diabetic patients. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.