ADAM17 expression in ACEI/ARB-treated patients with hypertension was comparable to that observed in patients without hypertension

BACKGROUND: ADAM17 (A disintegrin and metalloproteinase 17) contributes to angiotensin-converting enzyme (ACE) 2 shedding in response to angiotensin II-AT1 receptor signaling, potentially shifting the renin-angiotensin system toward its pressor arm. We investigated whether ACE inhibitor (ACEI) or AT1 receptor blocker (ARB) therapy modulates ADAM17 expression. METHODS: ADAM17 protein expression was evaluated by immunohistochemistry in alveolar type II pneumocytes of lung parenchymal samples from untreated control patients (n = 20) and patients treated with ACEI (n = 21) or ARB (n = 17; total ACEI/ARB-treated patients = 38). RESULTS: There were no significant differences in the proportion of ADAM17-expressing type II pneumocytes between patients without hypertension and ACEI/ARB-treated patients with hypertension (56.1 ± 4.3% vs 45.8 ± 3.1%, respectively). Similarly, no differences were observed according to smoking status (50.6 ± 4.1% in never smokers, 48.4 ± 4.0% in current smokers, and 50.8 ± 6.8% in former smokers) or sex (49.7 ± 4.2% in women vs. 49.1 ± 3.3% in men). In contrast, a significant age-related decline in the proportion of ADAM17-expressing type II pneumocytes was observed (56.2 ± 3.5% in patients <60 years vs. 43.0 ± 3.5% in patients ≥60 years; P = .005). CONCLUSIONS: These findings suggest that ACEI/ARB therapy, while targeting the pressor axis of the RAS, maintains ADAM17 expression at levels comparable to those in patients without hypertension. ACEI/ARB therapy may represent a potential strategy for the treatment of ADAM17-mediated cardiovascular, pulmonary, and inflammatory diseases.