No significant reduction in plasma cholesterol levels was observed in HCQ-treated mice compared with controls.<h4>Conclusion</h4>HCQ reduces aortic atherosclerosis in ApoE<sup>-/-</sup> mice, potentially through modulation of eNOS and HIF-1α expression, without exerting a beneficial effect on plasma cholesterol levels. The gene discussed is APOE; the disease is aortic atherosclerosis.