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.

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