O45-5 - DPP-4 Inhibition Ameliorates the Progression of Heart Failure after Transverse Aortic Constriction through Inhibition of Synthesis of Collagen Type III

Abstract

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral hypoglycemic agents. Role of DPP-4 on cardiac fibrosis after transverse aortic constriction (TAC) is not well known. Methods and Results: Wild-type mice and DPP-4 knockout (DPP-4KO) mice were subjected to TAC. Wild-type mice were then treated with vehicle (Control) or DPP-4 inhibitor (DPP-4i). DPP-4 activities in serum and myocardium were significantly increased at 2 weeks after TAC in Control group, but they were significantly decreased in DPP-4i group. The degree of cardiac hypertrophy was not different between three groups throughout the study. Fractional shortening was significantly higher in DPP-4i group and DPP-4KO group compared to Control group (Control, 36.4 ± 1.6%, DPP-4i, 40.4 ± 1.5%, DPP-4KO, 42.4 ± 0.3%, P < .05) at 4 weeks after TAC. The degree of myocardial fibrosis was significantly lower in DPP-4i group, DPP-4KO group compared to Control group (Control, 5.0 ± 0.7%, DPP-4i, 2.4 ± 0.3%, DPP-4KO, 2.3 ± 0.3%, P < .05) at 4 weeks after TAC by Masson trichrome staining. In transmission electron microscopy findings, there were no significant differences in structure of collagen fibrils between Control group and DPP-4KO group. The degree of collagen type III was decreased in DPP-4KO group compared with Control group (Control, 1.1 ± 0.2%, DPP-4KO, 0.4 ± 0.1%, P < .05) at 2 weeks after TAC by picrosirius red staining. Conclusion: DPP-4 inhibition ameliorates the progression of heart failure after TAC through inhibition of collagen type III.