Abstract 518: Cardioprotective Role of the Uncoupling Protein 3 Following Chronic Catecholamines Administration.
Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins sustaining an inducible proton conductance. Weakening the proton electrochemical gradient built up by the mitochondrial respiratory chain UCPs control the cellular energy balance and prevent oxidative stress. However, UCPs role in cardiac muscle has been poorly studied. To test UCP3 role in the heart, Wild Type and UCP3−/− mice underwent to a subcutaneous implantation of micro osmotic pumps to chronically deliver Isoproterenol (ISO 3 mg/Kg/die; WTiso, n = 6; UCP3KOiso, n = 7) or its vehicle (WTveh, n = 5; UCP3KOveh, n = 6). In all experimental groups we evaluated at basal condition and following 7 days of ISO administration: cardiac function by conscious echocardiography, UCP3 levels, βAdrenergic receptor density in myocardial plasma membrane fractions and ATP levels in myocardial cytosolic fractions. Following chronic catecholamine administration UCP3−/− mice showed a significant deterioration in cardiac function compared to WT mice evaluated by %Fractional Shortening (51 ± 5 % vs 63 ± 4 % , %FS, UCP3KOiso vs WTiso, p < 0.05). Moreover, chronic ISO administration led to a five fold increase in UCP levels in WT mice (WTveh vs WTiso, p < 0.05) showing for the first time a potential protective role in UCP3 signalling following chronic adrenergic stimulation in vivo. In contrast, ATP levels were significantly increased in UCP−/− mice compared to WT mice (56 ± 5 nM vs 43 ± 8 nM, UCP3KOiso vs WTiso, p < 0.05) suggesting an important role of UCP3 in regulating energy balance and potentially increasing oxidative stress in the heart in vivo following βadrenergic stimulation. In conclusion our data suggest for the first time in vivo an important protective role of UCP3 in cardiac stress following chronic adrenergic stimulation.