Although we show that increased soluble ACE2 achieved by DNA minicircles can attenuate diabetes-associated atherosclerosis, this finding differs from diabetes-associated kidney damage, previously reported in diabetic mice on an FVB/N background, which showed that ACE2 minicircles did not prevent kidney injury or dysfunction associated with diabetes, despite a significant increase in circulating ACE2 [25]. Here, ACE2 is linked to atherosclerosis.