In isolated hearts from male mice of the present study, Up4A still further decreased coronary flow in ApoE KO + HFD compared to WT mice (Emax 13.4 ± 0.8 mL/min/g in WT vs. 6.0 ± 0.8 mL/min/g in ApoE KO + HFD; P < 0.05 by two-way ANOVA, n = 3), suggesting Up4A-induced decrease in coronary flow is likely direct rather than via an indirect effect of endothelial dysfunction. The gene discussed is APOE; the disease is endothelial dysfunction.