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: Linnea Eriksson, Samuel Röhl, Robert Saxelin, Mariette Lengquist, Malin Kronqvist, Kenneth Caidahl, Claes-Göran Östenson, Anton Razuvaev
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 69 Issue 2 Pg. 101-109 (Feb 2017) ISSN: 1533-4023 [Electronic] United States
• PMID: 27875385 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Linagliptin

Topics

• Animals
• Blood Glucose (drug effects, metabolism)
• Carotid Artery Injuries (blood, drug therapy)
• Carotid Artery, External (drug effects, metabolism)
• Cell Proliferation (drug effects, physiology)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Dose-Response Relationship, Drug
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Linagliptin (pharmacology, therapeutic use)
• Male
• Random Allocation
• Rats
• Rats, Wistar
• Treatment Outcome
• Wound Healing (drug effects, physiology)