Document Detail

Iloprost reverses established fibrosis in experimental right ventricular failure.
MedLine Citation:
PMID:  25261325     Owner:  NLM     Status:  Publisher    
Prostacyclin and its analogues improve cardiac output and functional capacity in patients with pulmonary arterial hypertension (PAH); however, the underlying mechanism is not fully understood. We hypothesised that prostanoids have load-independent beneficial effects on the right ventricle (RV). Angio-obliterative PAH and RV failure were induced in rats with a single injection of SU5416 followed by 4 weeks of exposure to hypoxia. Upon confirmation of RV dysfunction and PAH, rats were randomised to 0.1 μg·kg(-1) nebulised iloprost or drug-free vehicle, three times daily for 2 weeks. RV function and treadmill running time were evaluated pre- and post-iloprost/vehicle treatment. Pulmonary artery banded rats were treated 8 weeks after surgery to allow for significant RV hypertrophy. Inhaled iloprost significantly improved tricuspid annulus plane systolic excursion and increased exercise capacity, while mean pulmonary artery pressure and the percentage of occluded pulmonary vessels remained unchanged. Rats treated with iloprost had a striking reduction in RV collagen deposition, procollagen mRNA levels and connective tissue growth factor expression in both SU5416/hypoxia and pulmonary artery banded rats. In vitro, cardiac fibroblasts treated with iloprost showed a reduction in transforming growth factor (TGF)-β1-induced connective tissue growth factor expression, in a protein kinase A-dependent manner. Iloprost decreased TGF-β1-induced procollagen mRNA expression as well as cardiac fibroblast activation and migration. Iloprost significantly induced metalloproteinase-9 gene expression and activity and increased the expression of autophagy genes associated with collagen degradation. Inhaled iloprost improves RV function and reverses established RV fibrosis partially by preventing collagen synthesis and by increasing collagen turnover.
Jose Gomez-Arroyo; Masahiro Sakagami; Aamer A Syed; Laszlo Farkas; Benjamin Van Tassell; Donatas Kraskauskas; Shiro Mizuno; Antonio Abbate; Harm J Bogaard; Peter R Byron; Norbert F Voelkel
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-26
Journal Detail:
Title:  The European respiratory journal     Volume:  -     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-27     Completed Date:  -     Revised Date:  2014-9-28    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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