Article

Endothelin-1 as initiator of epithelial-mesenchymal transition: potential new role for endothelin-1 during pulmonary fibrosis.

American Journal of Respiratory Cell and Molecular Biology (Impact Factor: 4.11). 08/2007; 37(1):1-2. DOI: 10.1165/rcmb.2007-0001ED
Source: PubMed
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    ABSTRACT: da pulmoner hipertansiyonun (PH) göreceli yüksek prevalansini (%30-40) açiklayabilecek ortak pa- tomekanizmalara sahiptir. PH özellikle, İAH hastalarinda egzersiz sinirlamasi ve kötü prognoza kat- kida bulunmaktadir. Spesifik klinik semptomlarin olmamasi çoğunlukla taninin geç konulmasina yol açmaktadir. Klinik karar ve difüzyon kapasitesindeki orantisiz düşüş yani sira, şiddetli hipok- semi veya egzersiz oksijen desatürasyonu, ekokardiyografi ve B-tipi natriüretik peptid (BNP) ve N- terminal pro-hormon BNP gibi biyo-belirteçler PH'un belirlenmesinde faydali araçlardir. Ancak ta- niyi doğrulamak için halen sağ kalp kateterizasyonu gereklidir. İAH hastalarinda PH'un yönetimi, altta yatan hastalik sürecinin tedavisi ile uzun süreli oksijen tedavisini içermektedir. Etkilenmiş hastalar, uygun olduğunda gecikmeksizin akciğer transplantasyon sirasina alinmalidir. Ancak yaş ve komorbiditeler nedeniyle İAH hastalarinin sadece küçük bir kismi akciğer transplantasyonuna uygun olacaktir. Birçok İAH'da tatmin edici tedavilerin yokluğu durumunda, etkilenen hastalarda PH'un klinik yükü de göz önüne alindiğinda, PAH için onaylanmiş olan spesifik vazomodülatör te- daviler İAH hastalari için umut verici olabilir. Sonuç olarak, İAH hastalarinda spesifik PH tedavisi- nin etkinliğini değerlendirmek için uygun olarak tasarlanmiş klinik çalişmalara acil ihtiyaç vardir.
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    ABSTRACT: Background: Pulmonary hypertension (PH) is associated with a poor prognosis in idiopathic pulmonary fibrosis (IPF). Endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) are important in both fibrosis and vascular remodeling. Objectives: We sought to determine the relationship between ET-1 and VEGF levels and hemodynamics in patients with IPF. We hypothesized that higher levels of ET-1 and VEGF would be associated with higher pulmonary artery pressures (PAP) and pulmonary vascular resistance (PVR) in patients with IPF. Methods: We performed a cross-sectional analysis of 52 adults with IPF enrolled in a prospective cohort with available clinical data, platelet-free plasma, and hemodynamics. ET-1 and VEGF levels were measured via immunoassay. The associations of ET-1 and VEGF with PAP and PVR were examined using generalized additive models adjusted for age, gender, race/ethnicity, and forced vital capacity (% predicted). Results: Sixteen of 52 (30.8%) had PH (mean PAP ≥25 mm Hg). After multivariable adjustment, higher ET-1 levels were significantly associated with higher systolic (p = 0.01), diastolic (p = 0.02), and mean (p = 0.01) PAP and possibly higher PVR (p = 0.09). There were no significant associations between VEGF levels and hemodynamics. Conclusions: Higher levels of ET-1 were associated with higher PAP and possibly higher PVR in participants with IPF. In a subgroup of patients, ET-1 may be a contributor to pulmonary vascular disease burden in IPF.
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    ABSTRACT: The fibrotic diseases encompass a wide spectrum of entities including such multisystemic diseases as systemic sclerosis, nephrogenic systemic fibrosis and sclerodermatous graft versus host disease, as well as organ-specific disorders such as pulmonary, liver, and kidney fibrosis. Collectively, given the wide variety of affected organs, the chronic nature of the fibrotic processes, and the large number of individuals suffering their devastating effects, these diseases pose one of the most serious health problems in current medicine and a serious economic burden to society. Despite these considerations there is currently no accepted effective treatment. However, remarkable progress has been achieved in the elucidation of their pathogenesis including the identification of the critical role of myofibroblasts and the determination of molecular mechanisms that result in the transcriptional activation of the genes responsible for the fibrotic process. Here we review the origin of the myofibroblast and discuss the crucial regulatory pathways involving multiple growth factors and cytokines that participate in the pathogenesis of the fibrotic process. Potentially effective therapeutic strategies based upon this new information are considered in detail and the major challenges that remain and their possible solutions are presented. It is expected that translational efforts devoted to convert this new knowledge into novel and effective antifibrotic drugs will be forthcoming in the near future.
    Biochimica et Biophysica Acta 12/2012; 1832(7). DOI:10.1016/j.bbadis.2012.12.007 · 4.66 Impact Factor