Linagliptin Modulation of Inflammation in Chronic Coronary Artery Disease.
Publication/Presentation Date
4-19-2025
Abstract
INTRODUCTION: Coronary artery disease (CAD) confers a continued challenge to healthcare necessitating innovative therapies. Linagliptin, a dipeptidyl peptidase 4 inhibitor, has been shown in preclinical and clinical studies to have cardioprotective effects independent of its glycemic control. An important pathway by which linagliptin has been described to induce these effects is due to its immune regulation. This study aims to evaluate the immune modulation by linagliptin treatment in a porcine model of chronic myocardial ischemia.
METHODS: Yorkshire swine underwent ameroid constrictor placement to the left circumflex artery, which induced chronic myocardial ischemia. Two wk later, swine either received no drug (n = 8) or 2.5 mg linagliptin daily (n = 8). Five weeks later, swine were sacrificed and left ventricular tissue was harvested. Protein expression and immune cell count was measured with immunoblotting and immunofluorescence, respectively. Data were statistically analyzed via Wilcoxon rank-sum test.
RESULTS: Linagliptin treatment was associated with decreased expression of inflammatory markers interleukin (IL)-1β (P = 0.0012), IL-6 (P = 0.0073), nuclear factor kappa B (NFκB) (P = 0.0106), transforming growth factor beta (P = 0.001), and IL-4 (P = 0.0419) in chronically ischemic myocardium. There was increased expression of phosphorylated NFκB at Ser536 (p=
CONCLUSIONS: Linagliptin treatment was associated with a reduction of proinflammatory cytokines in the setting of chronically ischemic myocardium, with identified modulation of the NFκB pathway. Following treatment, there was found to be an increase in CD11c expression, demonstrating an increase in dendritic cells as a possible immune modulating cell population within the ischemic myocardium.
Volume
309
First Page
146
Last Page
155
ISSN
1095-8673
Published In/Presented At
Muir, K. C., Harris, D. D., Stone, C., Kanuparthy, M., Broadwin, M., Hamze, J., Abid, M. R., & Sellke, F. W. (2025). Linagliptin Modulation of Inflammation in Chronic Coronary Artery Disease. The Journal of surgical research, 309, 146–155. Advance online publication. https://doi.org/10.1016/j.jss.2025.03.036
Disciplines
Medicine and Health Sciences
PubMedID
40253935
Department(s)
Fellows and Residents
Document Type
Article