Aims. In addition to its enzymatic function counterbalancing the pressor arm of the renin-angiotensin system (RAS), angiotensin-converting enzyme (ACE) 2 acts as the receptor for SARS-CoV-2. Viral fusion and cellular entry require ACE2 and the transmembrane protease serine 2 (TMPRSS2). Some evidence in tissue animals showed that RAS blockade by either ACE inhibitors (ACEIs) or type 1 angiotensin receptor blockers (ARBs) influence ACE2, though evidence in human lungs is lacking. Our aim was to evaluate ACE2 and TMPRSS2 in type II pneumocytes, the key cells that maintain lung homeostasis, present in lung parenchymal of ACEI/ARB-treated subjects compared to untreated control subjects.
Methods and Results. ACE2 and TMPRSS2 protein expression was evaluated by immunohistochemistry. The percentage of ACE2-expressing type II pneumocytes were not different between male and female. We found a significant interaction between ACEI/ARB treatment and smoking on ACE2-expressing type II pneumocytes (P = 0.026). Subjects with a positive history of smoking and ACEI/ARB treatment contained higher number of ACE2-expressing type II pneumocytes. Furthermore, ACE2 protein content correlated positively with smoking habits and age (P = 0.05). On the other hand, the percentage of TMPRSS2-expressing type II pneumocytes were higher in males than females (P = 0.026) and in subjects under 60 years of age (P = 0.04) and not significantly influenced by ACEI/ARB treatment (p=0.06). There was a positive association of TMPRSS2 protein content with age (P = 0.001) and smoking (P = 0.039) in ACEI/ARB-treated subjects with high TMPRSS2 protein levels most evident in ACEI/ARB-treated older adults and smokers.
Conclusions. We conclude that ACEI/ARB treatment influences human lung ACE2 and TMPRSS2 but this effect depends on the age and smoking habits of the subject.