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Linagliptin Modulation of Inflammation in Chronic Coronary Artery Disease

Kelsey C Muir1, Dwight D Harris1, Christopher Stone1

  • 1Department of Surgery, Division of Cardiothoracic Surgery, Warren Alpert Medical School, Brown University, Providence, Rhode Island; Cardiovascular Research Center, Rhode Island Hospital, Providence, Rhode Island.

The Journal of Surgical Research
|April 20, 2025
PubMed
Abstract

Insights

Linagliptin reduced inflammation in chronic myocardial ischemia by modulating the NFκB pathway and increasing CD11c dendritic cells. This offers a novel therapeutic approach for coronary artery disease.

Area of Science:

  • Cardiovascular Research
  • Immunology
  • Pharmacology

Background:

  • Coronary artery disease (CAD) remains a significant healthcare challenge requiring novel therapeutic strategies.
  • Linagliptin, a dipeptidyl peptidase 4 inhibitor, exhibits cardioprotective effects beyond glycemic control, potentially through immune modulation.
  • This study investigates linagliptin's immune-modulating effects in a porcine model of chronic myocardial ischemia.

Purpose of the Study:

  • To evaluate the immune modulation induced by linagliptin treatment in a porcine model of chronic myocardial ischemia.
  • To assess the impact of linagliptin on inflammatory markers and immune cell populations in ischemic heart tissue.

Main Methods:

  • Chronic myocardial ischemia was induced in Yorkshire swine using an ameroid constrictor.
  • Swine received either daily linagliptin (2.5 mg) or no drug for five weeks.
  • Left ventricular tissue was analyzed for protein expression (immunoblotting) and immune cell counts (immunofluorescence).

Main Results:

  • Linagliptin treatment significantly decreased expression of inflammatory markers including IL-1β, IL-6, NFκB, and TGF-β.
  • Increased expression of phosphorylated NFκB and IκBα was observed, indicating NFκB pathway modulation.
  • A significant increase in cluster of differentiation (CD) 11c expression and CD11c+ dendritic cell count was noted.

Conclusions:

  • Linagliptin treatment reduced proinflammatory cytokines in chronically ischemic myocardium.
  • The study identified modulation of the NFκB pathway and an increase in CD11c+ dendritic cells as key effects of linagliptin.
  • These findings suggest that linagliptin's immune-modulating properties, particularly involving dendritic cells, may contribute to its cardioprotective effects in CAD.
Keywords:
Coronary artery diseaseDendritic cellDipeptidyl peptidase-4 inhibitorInflammationIschemiaLinagliptin

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