کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5583958 1404282 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Changes in gene expression profiles in patients with pulmonary arterial hypertension associated with scleroderma treated with tadalafil
ترجمه فارسی عنوان
تغییرات در پروفایل های بیان ژن در بیماران مبتلا به فشار خون شریان ریوی همراه با اسکلرودرمی درمان شده با تادالافی
کلمات کلیدی
پرفشاری خون شریانی ریوی، اسکلروز سیستمیک، اسکلرودرمی، فشار خون شریانی ریوی مرتبط با اسکلرودرمی، مشخصات ژنی،
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیهوشی و پزشکی درد
چکیده انگلیسی

ObjectivePulmonary arterial hypertension (PAH) is one of the most devastating complications in scleroderma (SSc) patients and has a poorer outcome than other PAH subgroups. Tadalafil (Adcirca®) is a phosphodiesterase-5 inhibitor (PDE5-I) approved by the FDA for treatment of PAH; however, its effectiveness specifically in SSc-PAH patients is unclear. We investigated whether there were differences in gene expression associated with 16 weeks of treatment with tadalafil and, if so, whether these changes differed with respect to treatment outcome.MethodsWe enrolled 10 SSc-PAH subjects who were naïve to PDE5-I treatment, profiled gene expression in whole blood prior to and following treatment with tadalafil, measured changes in genomic profiles before and after treatment with tadalafil, and correlated them with changes in clinical outcomes, such as cardiopulmonary hemodynamics, six-min walk distance (6MWD), Borg Dyspnea Index (BDI), NYHA/WHO functional class (FC), B-type natriuretic peptide (BNP), and cardiac magnetic resonance imaging (cMRI).ResultsGenes associated with IL-12 signaling and extracellular matrix maintenance were coordinately up- or down-regulated with treatment, respectively, across all subjects. Interestingly, we found that genes encoding voltage-gated potassium channels and genes related to innate immunity were coordinately up-regulated in subjects who improved with tadalafil treatment compared to those patients who did not. In contrast, up-regulation of Golgi-related gene sets was associated with clinical worsening during the treatment period.ConclusionThe results of this pilot study suggest that outcomes of SSc-PAH patients treated with tadalafil are associated with specific changes in gene expression and biological pathways.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Seminars in Arthritis and Rheumatism - Volume 46, Issue 4, February 2017, Pages 465-472
نویسندگان
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