Sitagliptin protects diabetic rats with acute myocardial infarction through induction of angiogenesis: role of IGF-1 and VEGF.

Abstract

Angiogenesis is regulated in a tissue-specific manner in all patients, especially those with diabetes. In this study, we describe a novel molecular pathway of angiogenesis regulation in diabetic rats with myocardial infarction (MI) and examine the cardioprotective effects of different doses of sitagliptin. Male rats were divided into 5 groups: normal vehicle group, diabetic group, diabetic + MI, diabetic + MI + 5 mg/kg sitagliptin, and diabetic + MI + 10 mg/kg sitagliptin. Isoproterenol in diabetic rats resulted in significant (p < 0.05) disturbance to the electrocardiogram, cardiac histopathological manifestations, and an increase in inflammatory markers compared with the vehicle and diabetic groups. Treatment with sitagliptin improved the electrocardiogram and histopathological sections, upregulated vascular endothelial growth factor (VEGF) and transmembrane phosphoglycoprotein protein (CD34) in cardiac tissues, and increased serum insulin-like growth factor 1 (IGF-1) and decreased cardiac tissue homogenate for interleukin 6 (IL-6) and cyclooxygenase 2 (COX-2). A relationship was found between serum IGF-1 and cardiac VEGF and CD34 accompanied by an improvement in cardiac function of diabetic rats with MI. Therefore, the observed effects of sitagliptin occurred at least partly through an improvement in angiogenesis and the mitigation of inflammation. Consequently, these data suggest that sitagliptin may contribute, in a dose-dependent manner, to protection against acute MI in diabetic individuals.

• Authors: Dina M Khodeer, Shymaa E Bilasy, Noha E Farag, Amir E Mehana, Amani A Elbaz
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 97 Issue 11 Pg. 1053-1063 (Nov 2019) ISSN: 1205-7541 [Electronic] Canada
• PMID: 31116952 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Interleukin-6
• Vascular Endothelial Growth Factor A
• Insulin-Like Growth Factor I
• Cyclooxygenase 2
• Sitagliptin Phosphate

Topics

• Acute Disease
• Animals
• Blood Glucose (metabolism)
• Body Weight (drug effects)
• Cyclooxygenase 2 (metabolism)
• Diabetes Mellitus, Experimental (complications)
• Dose-Response Relationship, Drug
• Electrocardiography
• Heart Ventricles (drug effects, pathology)
• Insulin-Like Growth Factor I (metabolism)
• Interleukin-6 (metabolism)
• Male
• Myocardial Infarction (complications, metabolism, physiopathology, prevention & control)
• Neovascularization, Physiologic (drug effects)
• Organ Size (drug effects)
• Rats
• Sitagliptin Phosphate (pharmacology)
• Vascular Endothelial Growth Factor A (metabolism)