A Dipeptidyl Peptidase-4 Inhibitor but not Incretins Suppresses Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice.
Incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP) act to regulate appetite and body weight. Lately, reports have addressed on their emerging roles in the pathophysiology of atherosclerosis such as, their abilities to suppress atherosclerotic lesions in the aortic wall of apolipoprotein E-null mice, also exerting anti-inflammatory effects in vascular cells and monocytes/macrophages. Such findings observed by Kohashi K and others, led them also to study the effects of incretins in the pathophysiology of Abdominal Aortic Aneurysm (AAA), which shares risk factors with atherosclerosis and also coexist in a substantial amount of patients.
The authors, Kohashi K et al (2016) used male Apoe -/- mice to determine the effects of native incretins and Dipeptidyl Pepetidase-IV (DPP-IV) on ANG II-induced AAA and Atherosclerosis.
The authors subjected mice to atherogenic diets followed by treatments with ANG II, ANG II+GLP-1, ANG II+GIP and ANG II + DPP-IV Inhibitor. The Incretins used in the study, GLP -1 (7-36) amide and human GIP, were obtained from AnaSpec. Their results showed that, for the first time, it was a DPP-IV inhibitor and not the incretins (GIP, GLP) that prevented ANG II-induced AAA progression in the presence of atherosclerosis in the studied mouse model, essentially caused by the high dose of ANG II treatment. Among other evaluations done, the authors assessed atherosclerotic plaque formation with plaque burden assessments in the aortic area (Figure 3, Kohashi K et al, 2016), which helped with their conclusions.
Citation: Kohashi K, Hiromura M, Mori Y, Terasaki M, Watanabe T, Kushima H, Shinmura K, Tomoyasu M, Nagashima M, Hirano T. A Dipeptidyl Peptidase-4 Inhibitor but not Incretins Suppresses Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice. J Atheroscler Thromb. 2016; 23(4):441-54. doi: 10.5551/jat.31997.