ASSA13-03-22 The Relation Between Mitofusin-2 and b3-Adrenergic Receptor and Its Possible Mechanism in Chronic Heart Failure

Abstract

<h3>Objective</h3> To investigate the effects of β₃-adrenergic receptor (β₃-AR) on apoptosis and its possible mechanism of rats with isoproterenol (ISO)-induced chronic heart failure (HF). <h3>Methods</h3> (1) The rats were randomly divided into three groups: 7 weight– matched normal adult rats as controls, 18 rats with ISO induced heart failure and 21 rats with ISO induced heart failure but received SR59230A treatment for 6 weeks. (2) Echocardiography examinated left ventricular ejection fraction (EF), early peak diastolic velocity/late peak diastolic velocity (E/A), fractional shortening (FS), left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD). (3) Ratio of left ventricular weight and body weight (LVW/BW) was calculated. (4) The expression levels of β₃-AR, mitofusin-2 (Mfn2) and Caspase-3 mRNA in myocardium were detected by reverse transcriptio-polymerase chain reaction (RT-PCR). (5) The expression of β₃-AR, Mfn2, Caspase-, receptor serine/threonine kinases (Akt) and p-Akt protein were detected by western blot. <h3>Results</h3> (1) Compared with control group, the cardiac function of ISO group aggravated, LVW/BW and β₃-AR mRNA expression increased in heart failure rats; these changes significantly reduced in ISO+SR59230A group. (2) In ISO group, the expression of β₃-AR, Mfn2 and Caspase-3 protein rised as well as Akt decreased in relative to control group, myocardial apoptosis was significantly increased and that reverse significantly in ISO+SR59230A group. <h3>Conclusions</h3> In heart failure, the expression of β₃-AR increased, SR59230A inhibited β₃-AR and Mfn2, β₃-AR induced cardiomyocyte apoptosis through Mfn2. Mfn2 may become new therapeutic benefits with heart failure.