Document Detail

Inhibition of microRNA-17 Improves Lung and Heart Function in Experimental Pulmonary Hypertension.
MedLine Citation:
PMID:  22161164     Owner:  NLM     Status:  Publisher    
Rationale - MicroRNAs (miRs) control various cellular processes in tissue homeostasis and disease by regulating gene expression on the posttranscriptional level. Recently, it was demonstrated that the expression of miR-21 and members of the miR-17-92 cluster was significantly altered in experimental pulmonary hypertension (PH). Objective - We intend to evaluate the therapeutic efficacy and anti-remodeling potential of miR inhibitors in the pathogenesis of PH. Methods and Results - We first tested the effects of miR inhibitors (antagomirs), which were specifically designed to block miR-17 (A-17), miR-21 (A-21) and miR-92a (A-92a) in chronic hypoxia-induced PH in mice. A-17 and A-21 reduced right ventricular systolic pressure (RVSP) and all antagomirs decreased pulmonary arterial muscularization. However, only A-17 reduced hypoxia-induced right ventricular hypertrophy and improved pulmonary artery acceleration time (PAAT). Therefore, we additionally tested the effects of A-17 in monocrotaline-induced PH in rats. A-17 treatment significantly decreased RVSP and total pulmonary vascular resistance index, increased PAAcT, normalized cardiac output and decreased pulmonary vascular remodeling. Among the tested miR-17 targets, the cyclin-dependent kinase inhibitor 1A (p21) was upregulated in lungs undergoing A-17 treatment. Likewise, in human pulmonary artery smooth muscle cells, A-17 increased p21. Overexpression of miR-17 significantly reduced p21 expression and increased proliferation of smooth muscle cells. Conclusion - Our data demonstrate that A-17 improves heart and lung function in experimental PH by interfering with lung vascular and right ventricular remodeling. The beneficial effects may be related to the upregulation of p21. Thus, inhibition of miR-17 may represent a novel therapeutic concept to ameliorate disease state in PH.
Soni S Pullamsetti; Carmen Doebele; Ariane Fischer; Rajkumar Savai; Baktybek Kojonazarov; Bhola K Dahal; Hossein A Ghofrani; Norbert Weissmann; Friedrich Grimminger; Angelika Bonauer; Werner Seeger; Andreas M Zeiher; Stefanie Dimmeler; Ralph T Schermuly
Related Documents :
7315564 - Factors influencing the development of moyamoya phenomenon.
9009854 - Urokinase thrombolysis as initial therapy for acute and non-acute ischemic extremities.
9024924 - The effects of artery occlusion on temperature homogeneity during hyperthermia in rabbi...
8595014 - Severe raynaud's syndrome associated with interferon therapy. a case history.
7472964 - Hepatic artery ligation for hepatic vascular tumors with arteriovenous and arterioporta...
11206774 - Case report: outer sheath rupture may precede complete chordal rupture in fibrotic mitr...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-8
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  -     ISSN:  1535-4970     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Lung Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, bad nauheim, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Variable DNA methylation is associated with chronic obstructive pulmonary disease and lung function.
Next Document:  [Psychiatric side effects of deep brain stimulation in Parkinson's disease].