title: Effects of Linagliptin on Vessel Wall Healing in the Rat Model of Arterial Injury Under Normal and Diabetic Conditions.
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.
authors.affiliation: *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.
authors.forename: Linnea
authors.initials: L
authors.lastname: Eriksson
authors.forename: Samuel
authors.initials: S
authors.lastname: Röhl
authors.forename: Robert
authors.initials: R
authors.lastname: Saxelin
authors.forename: Mariette
authors.initials: M
authors.lastname: Lengquist
authors.forename: Malin
authors.initials: M
authors.lastname: Kronqvist
authors.forename: Kenneth
authors.initials: K
authors.lastname: Caidahl
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Östenson
authors.forename: Anton
authors.initials: A
authors.lastname: Razuvaev
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000097:blood / Q000188:drug therapy*; D002342:Carotid Artery, External / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069476:Linagliptin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000069476:Linagliptin