Long-Term Dipeptidyl-Peptidase 4 Inhibition Reduces Atherosclerosis and Inflammation via Effects on Monocyte Recruitment and Chemotaxis

Study Questions:

What is the effect of dipeptidyl-peptidase 4 (DPP-4) inhibition on atherosclerosis in mice?


Atherosclerotic-prone mice were treated with the DPP-4 inhibitor, alogliptin, or control vehicle for 12 weeks. Atherosclerosis quantification as well as metabolic, inflammatory, and vascular function studies were performed.


Alogliptin reduced atherosclerosis, and this was associated with a reduction in plaque macrophages. Alogliptin also improved markers of insulin resistance, reduced blood pressure, reduced visceral adipose tissue macrophage, and downregulated proinflammatory genes.


The authors concluded that alogliptin exerts antiatherosclerotic effects and reduces inflammation via inhibition of monocyte activation/chemotaxis.


Several previous large-scale studies have demonstrated that treating hyperglycemia is not sufficient to reduce the cardiovascular risk associated with diabetes. Thus, improved therapies are needed that not only target hyperglycemia, but also the underlying pathways that predispose diabetic patients to macrovascular events. DPP-4 is an enzyme that not only inactivates glucagon-like peptide 1, but also appears to have additional effects on inflammatory responses. Inhibition of DPP-4 may therefore have pleiotropic beneficial effects towards vascular disease, as demonstrated in this preclinical study. Hopefully, this will be the case in humans as well.

Clinical Topics: Heart Failure and Cardiomyopathies, Statins, Heart Failure and Cardiac Biomarkers

Keywords: Inflammation, Dipeptidyl Peptidase 4, Hyperglycemia, Uracil, Atherosclerosis, Macrophages, Diabetes Mellitus, Type 2, Vascular Diseases, Risk Factors, Blood Pressure, Insulin Resistance, Dipeptidyl-Peptidase IV Inhibitors, Intra-Abdominal Fat, Piperidines, Monocytes, Chemotaxis, Leukocyte, Glucagon-Like Peptide 1, Cardiovascular Diseases, Hypoglycemic Agents

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