Therefore, the current study was designed to investigate the mechanisms underlying combined HG and hyperlipidaemia‐induced ED by using both HUVEC and HMEC‐1 (in vitro) and LDL knockout mice CByJ.129S7(B6)‐Ldlrtm1Her/J (LDLR−/−) (in vivo) approaches. The gene discussed is LDLR; the disease is hyperlipidemia.