Linagliptin prevents left ventricular stiffening by reducing titin cleavage and hypophosphorylation.

摘要: The metabolic syndrome (MetS) is an escalating problem worldwide, causing left ventricular stiffening, early characteristic of diastolic dysfunction for which no treatment exists. As and stiffening in MetS patients are associated with increased circulating dipeptidyl peptidase-4 (DPP-4) levels, we investigated whether the clinically approved DPP-4 inhibitor linagliptin reduces stiffness MetS-induced cardiac disease. Sixteen-week-old obese ZSF1 rats, displaying stiffness, received linagliptin-supplemented or placebo diet four weeks. Linagliptin significantly reduced obesity, hyperlipidaemia, hyperglycaemia improved relaxation. This relaxation was related to decreased fibrosis cardiomyocyte passive (Fpassive ). Fpassive result titin isoform switching from stiff N2B more flexible N2BA phosphorylation total specifically its N2Bus region (S4080 S3391). Importantly, directly cleaved vitro, resulting , prevented by simultaneous administration linagliptin. In conclusion, improves rats preventing direct DPP4-mediated cleavage, as well modulating both levels phosphorylation. Reducing administering might prevent human.