Linagliptin, A Xanthine-Based Dipeptidyl Peptidase-4 Inhibitor, Ameliorates Experimental Autoimmune Myocarditis

This study sought to show the mechanism of how to ameliorate experimental autoimmune myocarditis (EAM) by administering dipeptidyl peptidase (DPP)-4 inhibitor linagliptin. The number of RAR-related orphan nuclear receptor gamma-positive Th17 cells infiltrated to the EAM myocardium was significantly attenuated by linagliptin treatment. Tandem mass spectrometry-based analysis demonstrated that DPP-4 binds to cathepsin G in EAM hearts, thereby protecting cathepsin G activity through inhibiting SerpinA3N activity. Linagliptin suppresses oxidative stress in EAM hearts as well. Thus, we found that DPP-4 plays a detrimental role in the progression of EAM by interacting with cathepsin G, which, in turn, suppresses SerpinA3N activity. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Automated summary

The study demonstrated the mechanism of ameliorating experimental autoimmune myocarditis by linagliptin, showing that it reduces Th17 cells infiltration and oxidative stress in EAM hearts. It also found that the interaction between DPP-4 and cathepsin G plays a detrimental role by suppressing SerpinA3N activity.