Previous research suggested that the presence of Cys18-Cys138 disulfide bond in human AGT, representing oxidized AGT, regulates Ang II production.62 However, loss of oxidized AGT did not affect atherosclerosis in mice.61 Of note, plasma AGT in mice is exclusively oxidized,61 whereas the oxidized form accounts for ≈50% to 60% plasma AGT in humans.62 In addition, AGT is considered to be the rate-limiting component of the RAS in mice,63 but renin is the rate-limiting enzyme to regulate Ang II production in humans. Here, REN is linked to atherosclerosis.