Role and mechanism of eicosapentaenoic acid in cardiac injury of diabetic cardiomyopathy

  AIM  To investigate the effects and mechanism of eicosapentaenoic acid (EPA) on cardiac functions in diabetic mice.

  METHODS  The mice were randomly divided into four groups: wild type mice group (Con), EPA intervention group (Con+EPA), diabetic group (DM), and diabetes EPA intervention group (DM+EPA). Diabetes was induced by intraperitoneal injections of STZ. The cardiac geometry and functions were assessed using transthoracic echocardiography. Wheat germ agglutinin (WGA) staining and TUNEL staining were performed to reveal the extent of myocyte hypertrophy and apoptosis. Expressions of cleaved caspase-3, Bax, Bcl-2, Dynamin-related protein 1(Drp1) and Phospho-AMP-activated protein kinase (p-AMPK) were detected using Western blot.

  RESULTS  The mice in DM group showed increase of left ventricular end-systolic diameter (LVESD) and left ventricular end diastolic diameter (LVEDD), reduction of left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS), increase of myocyte cross-sectional area and elevated apoptosis index, compared with those in Con group(P < 0.05). Western blot analysis also revealed accumulation of cleaved caspase-3, Bax and reduction of Bcl-2 in DM group compared with those in Con group. In addition, elevated p-AMPK/AMPK ratio and Drp1 expression were found in DM group compared with those in Con group(P < 0.05). However, the administration of EPA significantly increased LVEF and LVFS, decreased LVESD, LVEDD, myocardial cross-sectional area and apoptosis index in DM mice(P < 0.05). The administration of EPA in DM mice decreased cleaved caspase-3 and Bax expression, increased Bcl-2expression, improved p-AMPK/ AMPK ratio and reduced Drp1 expression(P < 0.05).

  CONCLUSION  EPA alleviates diabetes-induced cardiac dysfunction by inhibiting myocyte hypertrophy and apoptosis and the attributed mechanism involves, at least in part, AMPK/Drp1 signaling.