Profibrosing effect of angiotensin converting enzyme inhibitors in human lung fibroblasts

Lung. 2015 Apr;193(2):199-202. doi: 10.1007/s00408-015-9688-8. Epub 2015 Feb 6.

Abstract

Objective: The objective of this study is to determine the effect of two angiotensin-converting enzyme inhibitors (ACEi) (Enalapril and Captopril), an angiotensin-II receptor inhibitor (Losartan) and a renin inhibitor (Aliskiren) on renin, TGF-β1 and collagen expressions in human lung fibroblast cultures through real-time PCR and ELISA.

Materials and methods: Normal commercial fibroblasts (CCD25) were exposed to 10(-6) M of enalapril, captopril, losartan, or aliskiren for 6 h. Subsequently, media were recovered and proteins were concentrated; RNA was extracted from the cells. Real time-PCR and ELISA were performed.

Results: ACEi and losartan-stimulated fibroblasts showed an increase in the expression of TGF-β1, Collagen-Iα1 (Col-Iα1), and renin (except losartan) vs PolR2A (p < 0.05), and upregulation of TGF-β1 protein (p < 0.01), except with aliskiren.

Conclusion: Results show that ACEis and losartan could play a profibrosing role by inducing the overexpression of molecules such TGF-β1 and Collagen.

MeSH terms

  • Amides / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Captopril / pharmacology
  • Cells, Cultured
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Enalapril / pharmacology
  • Fibroblasts / drug effects*
  • Fibroblasts / pathology
  • Fibrosis
  • Fumarates / pharmacology
  • Humans
  • Losartan / pharmacology
  • Lung / pathology*
  • Protein Biosynthesis / drug effects
  • Renin / antagonists & inhibitors
  • Renin / genetics
  • Renin / metabolism
  • Transcription, Genetic / drug effects*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Amides
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Fumarates
  • Transforming Growth Factor beta1
  • aliskiren
  • Enalapril
  • Captopril
  • Renin
  • Losartan