Abstract
AntimiR‐145 therapy improves right ventricular structure in experimental pulmonary arterial hypertension (1090.1)
The FASEB journal, Vol.28(S1), p.n/a
04/2014
DOI: 10.1096/fasebj.28.1_supplement.1090.1
Abstract
Abstract only Our previous work shows miRNA‐145 is increased in pulmonary arterial hypertension (PAH) and knockdown of miR‐145 in rats exposed to Sugen‐5416, hypoxia, and normoxia, repairs pulmonary arteriopathy and improves RV function. One explanation for improvements is that partial repair of the arteriopathy reduces pulmonary arterial pressure (and/or increases vascular compliance) which reduces RV afterload. Normal repair mechanisms regulating cardiac structure may then result in reduced RV hypertrophy at the cellular and tissue levels. To test this we measured ventricular weights, RV myocyte cross‐sectional areas and collagen deposition. AntimiR‐145 produced a modest decrease in the RV/LV+S ratio as well as decreased RV weight/body weight ratio. Interestingly, the positive effect on tissue mass was not a result of normalizing RV cardiomyocyte hypertrophy because cellular cross‐sectional area was unaffected by antimiR‐145. These results are more consistent with the response to antimiR‐145 being a reduction in cell number and tissue mass rather than cell atrophy. The therapeutic response also includes beneficial effects on matrix remodeling as shown by reduced collagen deposition. Together the results demonstrate subchronic treatment with antimiR‐145 has beneficial cardiac effects in rats with PAH that result in increased cardiac output as well as partial regression of RV hypertrophy and matrix remodeling. Grant Funding Source : Supported by NIH grant HL097220 to WTG and AHA fellowship 13PRE17070053 to JMM.
Details
- Title: Subtitle
- AntimiR‐145 therapy improves right ventricular structure in experimental pulmonary arterial hypertension (1090.1)
- Creators
- Jared McLendon - University of South AlabamaSachindra Joshi - University of South AlabamaJason Fewell - Egen, Inc Huntsville AL United StatesMasahiko Oka - University of South AlabamaIvan McMurtry - University of South AlabamaWilliam Gerthoffer - University of South Alabama
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.28(S1), p.n/a
- DOI
- 10.1096/fasebj.28.1_supplement.1090.1
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Language
- English
- Date published
- 04/2014
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984618621702771
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