Analysis of the Correlation between the Myocardial Expression of DPP-4 and the Clinical Parameters of Patients with Heart Failure

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as antidiabetic drugs. We recently reported that DPP-4 inhibition has beneficial effects on heart failure (HF) mice model. Furthermore, we confirmed that myocardial DPP-4 activity was significantly increased in HF mice compared with non-HF mice. The aim of this study was to investigate the level of myocardial CD26 (DPP-4) expression and its association to clinical parameters in HF patients.Endomyocardial biopsy (EMB) specimens (n = 33) were obtained from HF patients who were admitted to Chiba University Hospital from June 2006 to July 2012. EMB specimens were fixed in formaldehyde and stained with Masson's trichrome staining or with anti-CD26 antibody. Patients were divided into the high CD26 density (CD26-H) or low CD26 density groups (CD26-L). DPP-4 density was compared with blood brain natriuretic peptide (BNP) level and echocardiographic parameters at one year after EMB. Although there were no significant differences in echocardiographic parameters between the CD26-H group and CD26-L group, blood BNP levels were higher in the CD26-H group than in the CD26-L group at one year after EMB. Multivariate regression analysis showed that CD26 density was also an independent determinant of blood BNP levels at one year after EMB.The level of myocardial CD26 expression might be a predictive marker of prognosis in patients with HF. (Int Heart J 2018; 59: 1303-1311

Pharmacological Inhibition of Serine Proteases to Reduce Cardiac Inflammation and Fibrosis in Atrial Fibrillation

“…Dipeptidyl-peptidase-4 (DPP4) is a serine protease expressed in several cell types and organs, which is known to cleave and inactivate the incretin glucagon-like peptide-1 (GLP-1). In the heart, DPP4 is mainly expressed in the membrane of the capillary endothelium, in the sarcolemma of cardiomyocytes and is also produced by infiltrating macrophages (Kobara, 2018;Gorrell, 2005). Oral DPP4 inhibitors (gliptins) are used in type-2 diabetes to potentiate GLP-1 signaling.…”