Transfat‐mediated apoptosis is regulated by autophagy in primary cardiac myofibroblasts

Abstract only Dietary trans fatty acids (TFA) are linked to cardiovascular disease which has led to recommendations to remove TFAs from diet. We investigated the effects of two common fatty acids ‐ vaccenic acid (VA ‐ found in dairy products), and elaidic acid (EA ‐ found in hydrogenated vegetable oils) on cell death in primary rat ventricular myofibroblasts (rVF). VA‐ and EA‐treated cells exhibited apoptotic cell death in rVF, as reflected in MTT and FACS assays. A significant reduction in mitochondrial membrane potential and an increase in the Bax/Bcl2 ratio and Bax translocation to the mitochondria was found suggesting apoptosis in the presence of TFA. Elevated cleaved caspase‐9 and caspase‐3 (without caspase‐8), shows that EA and VA treatments induce caspase‐dependent apoptosis. Transmission electron microscopy reveals autophagosome formation and lysosome activation in VA and EA treated rVF. Induction of autophagy markers including LC3‐B lipidation, increased Atg5‐12 formation and increased beclin‐1 were observed confirming autophagy activation by EA and VA. Inhibition of ATG3 and ATG5 significantly inhibited cytotoxic effects by preventing caspase‐3 and caspase‐7 activation in EA and VA treated rVF. In conclusion we show that TFAs induce apoptosis and autophagy in rVF and that TFA‐induced autophagy is required for this proapoptotic effect. Supported by CIHR and DFC.