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Objective Recent reports have implicated the p53 tumor suppressor in the regulation of lipid metabolism. We hypothesized that the pharmacological activation of p53 with low-dose doxorubicin, which is widely used to treat several types of cancer, may have beneficial effects on nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Methods We used long-term pharmacological activation of p53 by i.p. or oral administration of low-dose doxorubicin in different animal models of NAFLD (high fat diet containing 45% and 60% kcal fat) and NASH (methionine- and choline-deficient diet and choline deficiency combined with high fat diet). We also administered doxorubicin in mice lacking p53 in the liver and in two human hepatic cells lines (HepG2 and THLE2). Results The attenuation of liver damage was accompanied by the stimulation of fatty acid oxidation and decrease of lipogenesis, inflammation, and ER stress. The effects of doxorubicin were abrogated in mice with liver-specific ablation of p53. Finally, the effects of doxorubicin on lipid metabolism found in animal models were also present in two human hepatic cells lines, in which the drug stimulated fatty acid oxidation and inhibited de novo lipogenesis at doses that did not cause changes in apoptosis or cell viability. Conclusion These data provide new evidence for targeting p53 as a strategy to treat liver disease., Highlights • Intraperitoneal and oral low-dose doxorubicin ameliorates NAFLD and NASH in animal models. • Doxorubicin requires p53 for its hepatic actions. • Doxorubin decreases lipid content in human hepatocytes without affecting cell viability and apoptosis.

INTRODUCTION: Real-world, country-specific studies of dual antiplatelet therapy (DAPT) duration among survivors of acute coronary syndrome (ACS) are important for improving long-term prognosis. AIMS: To investigate DAPT duration after hospital discharge for ACS in Spain. RESULTS: Data from patients enrolled in the Spanish cohort of the EPICOR (long-tErm follow-up of antithrombotic management Patterns In acute CORonary syndrome patients) study (NCT01171404) were analyzed for changes to antithrombotic medication up to 2 years postdischarge according to index event diagnosis and patient characteristics. Deaths, coronary events, and bleeding events were analyzed over the same period. Overall, a high proportion of patients remained on DAPT at 2 years (53.1%). Among patients who experienced any on-treatment bleeding event, almost two-thirds remained on DAPT at the end of follow-up. Patients >65 years, diabetic, or those that were medically managed were more likely to continue with DAPT until 2 years following discharge. At 2 years, the incidence of bleeding events requiring hospitalization was low compared with the incidence of coronary events (1.4% vs 6.6%). There was a numerical reduction in coronary events, but no increase in bleeding events, with DAPT continuation compared with single antiplatelet therapy. CONCLUSIONS: More than half of patients in this unselected cohort study remained on DAPT at 2 years following discharge for ACS. Continuation with DAPT was greater among patients with additional cardiovascular risk factors, which suggests that treating physicians in Spain prioritizes ischemic risk reduction over bleeding risk in patients with ACS, according to patient's risk profile.