Abstract 13024: Dipeptidyl Peptidase Iv Inhibition Improves Chamber Compliance and Reduces Lv Hypertrophy in a Rodent Model of Myocardial Infarction With Diabetes
Following myocardial infarction (MI), individuals with diabetes have a 2-fold increase in the risk of heart failure, due in part to excessive loss of cardiac microvasculature. Restitution of the microvasculature is mediated by the migration of endothelial progenitor cells in response to SDF-1, a chemokine that is elaborated by ischemic tissue but rapidly degraded by dipeptidyl-peptidase 4 (DPP-4).
Methods: 8 week old Fischer rats with streptozotocin induced diabetes (2 weeks duration) were randomised to receive vehicle or the DPP-4 inhibitor, sitagliptin (300 mg/kg/daily gavage). Two weeks later animals underwent experimental MI, induced by ligation of the left anterior descending coronary artery. Structure (myocyte hypertrophy and capillary density) and function (echocardiography and pressure volume loops) were examined 6 weeks post-MI.
Results: At two days post MI, infarct size and fractional shortening, as assessed by echocardiography was not different between groups (p=NS). Six weeks following MI, untreated diabetic rats developed both systolic and diastolic cardiac dysfunction, in association with capillary loss, fibrosis and myocyte hypertrophy (all p<0.01). Without affecting plasma glucose, sitagliptin treatment reduced LV mass, improved diastolic function (improved slope of the end diastolic pressure volume relationship), increased capillary density and reduced myocyte hypertrophy (all p < 0.05). Infarct size, systolic blood pressure and systolic function were not altered by DPP-IV inhibition.
Conclusion: This study shows that DPP-4 inhibition with sitagliptin attenuates cardiac hypertrophy, increases capillary density and improves cardiac chamber compliance in the post-MI setting. DPP-4 inhibition may be a novel therapeutic strategy in diabetes to improve outcomes post MI.
- © 2011 by American Heart Association, Inc.