Table 2.

The effect of RAAS blockers on ACE2 expression in clinical study.

Source	Participants	Effect of RAAS blockers on ACE2
Wang G [60], 2008	50 patients with diabetic nephropathy: 26 were being treated by ACEI alone, the other 24 by ACEI and ARB.	The use of ACEIs alone and ACEIs+ARBs did not increase urine ACE2 expression after 12 weeks.
Soro-Paavonen [61], 2012	Quantitative ACE2 activity in serum was measured among 859 type 1 diabetes patients and 204 healthy controls.	ACE2 activity was increased in male (10%) and female (20%) diabetes patients who were on ACEIs treatment. However, ACE2 activity was increased by ARBs use in female patients not male diabetes patients.
Vuille-dit-Bille [62], 2015	46 patients, of which 9 were under ACEI and 13 ARB treatment.	ACEIs not ARBs increased intestinal mRNA levels of ACE2 by 1-fold in patients.
Sama [63], 2020	ACE2 concentrations were measured in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort).	In the index cohort, use of ACEIs, or ARBs was not an independent predictor of plasma ACE2. In the validation cohort, ACEIs (estimate = −0.17, P = 0.002) and ARBs use (estimate = −0.15, P = 0.03) were independent predictors of lower plasma ACE2.
Milne [64], 2020	The gene expressions of ACE2 and two host cell proteases, TMPRSS2 and ADAM17, were evaluated in 1051 lung tissue samples from the Human Lung Tissue Expression Quantitative Trait Loci Study (Lung eQTL Study).	ACEI use was associated with significantly lower ACE2 and TMPRSS2 expression, but was not associated with ADAM17 expression. ARBs were not associated with altered expression of these three genes.