Is losartan the drug for all seasons?

Mount Sinai School of Medicine, New York, USA.
Current Opinion in Pharmacology (Impact Factor: 4.6). 03/2012; 12(2):223-4. DOI: 10.1016/j.coph.2012.02.007
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Available from: Francesco Ramirez, Oct 28, 2014
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    • "Losartan, a small-molecule angiotensin II type 1 receptor antagonist used to treat hypertension, was shown to reduce TGF-b expression and myocardial fibrosis in mice with hypertrophic cardiomyopathy (Lim et al, 2001). Subsequently, the efficacy in reducing mechano-and TGF-b-mediated ECM remodeling of aortic roots and heart walls in Marfan syndrome was established (Habashi et al, 2006; Ramirez & Rifkin, 2012; Pees et al, 2013; Cook et al, 2014). The primary effect of losartan on tissue remodeling in Marfan syndrome is likely to be mechanosensitive, mediated through reduction in blood pressure, since treatment with b1 receptor antagonists slows aortic dilatation to a similar degree as losartan (Lacro et al, 2014). "
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    ABSTRACT: Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)-a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
    Full-text · Article · Jul 2015 · EMBO Molecular Medicine