Profibrosing effect of angiotensin converting enzyme inhibitors in human lung fibroblasts

Area of Science:

• Pharmacology
• Cell Biology
• Fibrosis Research

Background:

• The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in regulating blood pressure and fluid balance.
• Dysregulation of the RAAS is implicated in various fibrotic diseases, including lung fibrosis.
• Understanding the direct effects of RAAS inhibitors on lung fibroblasts is essential for evaluating their profibrotic potential.

Purpose of the Study:

• To investigate the impact of angiotensin-converting enzyme inhibitors (ACEi) like enalapril and captopril, an angiotensin-II receptor inhibitor (losartan), and a renin inhibitor (aliskiren) on key fibrotic markers in human lung fibroblasts.
• To quantify changes in renin, transforming growth factor-beta 1 (TGF-β1), and collagen expression.

Main Methods:

• Human lung fibroblasts (CCD25) were treated with 10(-6) M of enalapril, captopril, losartan, or aliskiren for 6 hours.
• Messenger RNA (mRNA) and protein levels of renin, TGF-β1, and collagen were analyzed using real-time PCR and ELISA.
• Polyester RNA polymerase II subunit A (PolR2A) served as a reference gene.

Main Results:

• Treatment with ACEi (enalapril, captopril) and losartan significantly increased the expression of TGF-β1, Collagen-Iα1 (Col-Iα1), and renin mRNA compared to the control.
• Losartan did not increase renin expression.
• TGF-β1 protein levels were upregulated by ACEi and losartan, but not by aliskiren.

Conclusions:

• ACE inhibitors and losartan may exert a profibrotic effect on human lung fibroblasts.
• These drugs appear to induce overexpression of TGF-β1 and collagen, potentially contributing to fibrotic processes.
• Aliskiren did not show a similar profibrotic effect on TGF-β1 protein expression in this model.