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Indeed, although many studies have clearly shown that several interventions including pharmacological therapy and lifestyle modifications improve endothelial function under the condition of relatively mild vascular endothelial dysfunction [8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35], we have shown that advanced endothelial dysfunction is not reversible even by appropriate pharmacological therapy [94]