Abstract 11995: Auraptene, a Citrus Flavonoid, Prevents the Worsening of Systolic Function Following Myocardial Infarction in Rats
Introduction: Heart failure is associated with pathological growth of constituent cardiomyocytes. To achieve effective oral pharmacological therapy for heart failure, we screened natural compounds purified from a citrus fruits library. We reported that auraptene isolated from the peel of citrus fruit (Citrus Hassaku) inhibits cardiomyocyte hypertrophy in culture.
Hypothesis: We investigated whether auraptene from the citrus fruit improved the development of heart failure in rats with myocardial infarction (MI).
Methods and Results: 1) In neonatal rat cardiomyocytes, auraptene, at the concentrations of 2.5, or 10 μM, dose-dependently repressed phenylephrine-induced hypertrophic responses such as myofibrillar organization, increase in cell size and the transcriptional activations of ANF and ET-1. 2) Adult rats were subjected to sham operation or MI. One week later, twenty-two rats with a moderate size of MI (FS≤40%) were then randomly assigned to vehicle (n=8), auraptene low-dose (5 mg/kg/day, n=7), or high-dose (50 mg/kg/day, n=7). Oral daily treatments with these agents were continued for 6 weeks. There were no differences in LV geometric and functional data among the 3 MI groups before treatment. After treatment, LVFS was significantly higher in the auraptene low-dose (21%) and high-dose (26%) groups than the vehicle group (16%). LV wall thickness in the remote non-infarct area was significantly thinner in the auraptene low-dose (1.4 mm) and high-dose (1.2 mm) groups than the vehicle group (2.5 mm). Histological analysis showed that auraptene treatment significantly inhibited MI-induced increases in myocardial cell diameter and perivascular fibrosis compared with vehicle treatment. Moreover, the mRNA levels of ANF and ET-1 from left ventricle were also reduced in the auraptene group compared with in vehicle treatment.
Conclusions: Auraptene treatment dose-dependently prevents the worsening of LV systolic function and represses hypertrophy in the non-infarct area after MI in adult rats. A natural compound, auraptene is expected as a novel useful agent for heart failure therapy in humans.
- © 2013 by American Heart Association, Inc.