Abstract:
BACKGROUND:Cardiac fibrosis occurs because of disruption of the extracellular matrix network leading to myocardial dysfunction. Angiotensin II has been implicated in the development of cardiac fibrosis. Recently, microRNAs have been identified as an attractive target for therapeutic intervention in cardiac pathologies; however, the underlying mechanism of microRNAs in cardiac fibrosis remains unclear. MicroRNA-130a (miR-130a) has been shown to participate in angiogenesis and cardiac arrhythmia; however, its role in cardiac fibrosis is unknown. METHODS AND RESULTS:In this study, we found that miR-130a was significantly upregulated in angiotensin II-infused mice. The in vivo inhibition of miR-130a by locked nucleic acid- based anti-miR-130a in mice significantly reduced angiotensin II-induced cardiac fibrosis. Upregulation of miR-130a was confirmed in failing human hearts. Overexpressing miR-130a in cardiac fibroblasts promoted profibrotic gene expression and myofibroblasts differentiation, and the inhibition of miR-130a reversed the processes. Using the constitutive and dominant negative constructs of peroxisome proliferator-activated receptor γ 3-'untranslated region (UTR), data revealed that the protective mechanism was associated with restoration of peroxisome proliferator-activated receptor γ level leading to the inhibition of angiotensin II-induced cardiac fibrosis. CONCLUSIONS:Our findings provide evidence that miR-130a plays a critical role in cardiac fibrosis by directly targeting peroxisome proliferator-activated receptor γ. We conclude that inhibition of miR-130a would be a promising strategy for the treatment of cardiac fibrosis.
journal_name
J Am Heart Assocjournal_title
Journal of the American Heart Associationauthors
Li L,Bounds KR,Chatterjee P,Gupta Sdoi
10.1161/JAHA.117.006763subject
Has Abstractpub_date
2017-11-07 00:00:00issue
11issn
2047-9980pii
JAHA.117.006763journal_volume
6pub_type
杂志文章abstract::Background Stroke is a leading cause of death and disability in the Middle East. Data on the uptake of evidence-based practices are limited in the region. We aimed to examine patterns of stroke presentation, management, and outcomes at public Palestinian hospitals. Methods and Results Comprehensive data from all patie...
journal_title:Journal of the American Heart Association
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journal_title:Journal of the American Heart Association
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更新日期:2013-06-10 00:00:00
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