Long noncoding RNA H19 in the pathogenesis of right ventricular failure with pulmonary arterial hypertension
J. Omura (Quebec city, Canada), S. Breuils-Bonnet (Quebec city, Canada), O. Boucherat (Quebec city, Canada), S. Provencher (Quebec city, Canada), S. Bonnet (Quebec city, Canada)
Source: International Congress 2018 – Pathobiology of pulmonary hypertension
Session: Pathobiology of pulmonary hypertension
Session type: Poster Discussion
Number: 3933
Disease area: Pulmonary vascular diseases
Abstract Background : Right ventricular (RV) failure is an important prognostic factor for pulmonary arterial hypertension (PAH). RV failure in PAH is associated with increased ischemia and decreased RV wall perfusion due to repressing angiogenesis and remodeled coronary circulation. The mechanism of RV failure remains poorly understood. Recently the role of H19, a long noncoding RNA highly expressed in the heart, has been investigated in left ventricular failure. Its role in RV remains unknown.
Methods and Results : Using Taq-Man qRT-PCR, we demonstrated that H19 and its mature product miR-675 were up-regulated in RVs (but not in the LVs) from PAH patients compared to those from controls (n=8 each). In addition, H19 was negatively correlated with cardiac index. Interestingly H19 expression was not changed in lung of PAH patients compare to control. Similar findings were obtained in the PAH monocrotaline rat model. From a mechanistic point of view we showed that H19 upregulation in PAH RV was associated with repression of its targets calcium/calmodulin-dependent protein kinase II d (a critical regulator of MEF2 signaling which is implicated in heart failure) and AKT signaling (a major regulator of NFAT signaling implicated in cardiac hypertrophy and angiogenesis) in the RVs from PAH patients (western blot, n=8-9, all p<0.05).
Conclusions : We demonstrated for the first time that H19 upregulation is associated with RV failure due to PAH, which could potentially lead to RV-specific novel biomarkers and therapeutic targets.
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J. Omura (Quebec city, Canada), S. Breuils-Bonnet (Quebec city, Canada), O. Boucherat (Quebec city, Canada), S. Provencher (Quebec city, Canada), S. Bonnet (Quebec city, Canada). Long noncoding RNA H19 in the pathogenesis of right ventricular failure with pulmonary arterial hypertension. 3933
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