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

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.

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).

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).

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.