Losartan Halts Smoke-Related Lung Damage in Mice

Inhibition of TGF-β normalizes smoke-induced TFG-β signaling and prevents alveolar cell death

TUESDAY, Jan. 10 (HealthDay News) -- Losartan, an angiotensin receptor type 1 blocker used to antagonize transforming growth factor (TGF)-β, can prevent cigarette smoke (CS)-induced lung damage in a mouse model, according to a study published in the Jan. 3 issue of the Journal of Clinical Investigation.

Megan Podowski, of the Johns Hopkins University School of Medicine in Baltimore, and colleagues investigated whether inhibiting TGF-β signaling would protect against CS-induced lung injury. Mice were either exposed to CS or kept unexposed (controls); they were treated with low-dose or high-dose losartan, or a TGF- β neutralizing antibody. Human lung tissue from individuals with chronic obstructive pulmonary disease (COPD) and at-risk controls were obtained, and the morphometry and histochemistry was investigated.

The researchers found that TGF-β was induced in mice exposed to CS and patients with COPD. In CS-exposed mice, there was CS-induced alveolar cell apoptosis due to enhanced TGF-β-signaling. TGF-β-signaling and alveolar cell death were neutralized by systemic administration of a TGF-β specific neutralizing antibody. Oxidative stress, inflammation, metalloprotease activation, and elastin remodeling were improved with use of losartan.

"Inhibition of TGF-β signaling through angiotensin receptor blockade can attenuate CS-induced lung injury in an established murine model. More importantly, our findings provide a preclinical platform for the development of other TGF-β-targeted therapies for patients with COPD," the authors write.

Full Text

Copyright © 2012 HealthDay. All rights reserved.

Powered by

jQuery UI Accordion - Default functionality

For life-long learning and continuing professional development, come to Lippincott's NursingCenter.

Nursing Jobs Plus
Featured Jobs
Recommended CE Articles Recommended Nursing Articles Evidence Based Practice Skin Care Network NursingCenter Quick Links What’s Trending Events