A novel role of endothelial autophagy as a regulator of myocardial fatty acid oxidation.

BACKGROUND: We sought to determine if endothelial autophagy affects myocardial energy metabolism.

METHODS: We used isolated working mouse hearts to compare cardiac function, energy metabolism, and ischemic response of hearts from endothelial cell-specific ATG7 knockout (EC-ATG7-/- ) mice to hearts from their wild-type littermates. We also conducted gene analyses on human umbilical vein endothelial cells incubated with scrambled small interfering RNA or small interfering ATG7.

RESULTS: In the presence of insulin, working hearts from EC-ATG7-/- mice, relative to those from wild-type littermates, exhibited greater reductions in insulin-associated palmitate oxidation indicating a diminished reliance on fatty acids as a fuel source. Likewise, palmitate oxidation was markedly lower in the hearts of EC-ATG7-/- mice versus wild-type mice during reperfusion of ischemic hearts. Although hearts from EC-ATG7-/- mice revealed significantly lower triacylglycerol content compared with those from wild-type mice, ATG7-silenced human umbilical vein endothelial cells demonstrated appreciably lower fatty acid binding protein 4 and 5 expression relative to those treated with scrambled small interfering RNA.

CONCLUSIONS: Disruption of endothelial autophagy reduces cardiac fatty acid storage and dampens reliance on fatty acid oxidation as a cardiac fuel source. The autophagy network represents a novel target for designing new strategies aimed at resetting perturbed myocardial bioenergetics.