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AntimiR‐145 therapy improves right ventricular structure in experimental pulmonary arterial hypertension (1090.1)
Author(s) -
McLendon Jared,
Joshi Sachindra,
Fewell Jason,
Oka Masahiko,
McMurtry Ivan,
Gerthoffer William
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1090.1
Subject(s) - cardiology , muscle hypertrophy , medicine , afterload , right ventricular hypertrophy , pulmonary hypertension , pulmonary artery , pressure overload , myocyte , cardiac hypertrophy , hemodynamics
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.