In addition, growing evidence supports that 2-methoxyestradiol (2-ME), a natural estrogen metabolite produced by COMT, has a potent antiproliferative and antiangiogenic capacity [38], [39] and has direct involvement in redox-regulated signaling as a pro-oxidant [44], thus it could be a possible disease mechanism in the protection against atherosclerosis development. Here, COMT is linked to atherosclerosis.