Farnesoid-X-receptor expression in monocrotaline-induced pulmonary arterial hypertension and right heart failure

• FXR was expressed in rat lung and heart tissues.
• FXR expression increased sharply in the lung tissues of PAH and RHF rats.
• FXR expression was reduced in PAH and RHF rat RV tissue.
• FXR expression was unaltered in PAH LV but reduced in RHF rat LV tissue.
• FXR expression was prominent in the neovascularization region.

ObjectiveThe farnesoid-X-receptor (FXR) is a metabolic nuclear receptor superfamily member that is highly expressed in enterohepatic tissue and is also expressed in the cardiovascular system. Multiple nuclear receptors, including FXR, play a pivotal role in cardiovascular disease (CVD). Pulmonary arterial hypertension (PAH) is an untreatable cardiovascular system disease that leads to right heart failure (RHF). However, the potential physiological/pathological roles of FXR in PAH and RHF are unknown. We therefore compared FXR expression in the cardiovascular system in PAH, RHF and a control.Methods and resultsHemodynamic parameters and morphology were assessed in blank solution-exposed control, monocrotaline (MCT)-exposed PAH (4 weeks) and RHF (7 weeks) Sprague–Dawley rats. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blot (WB), immunohistochemistry (IHC) analysis and immunofluorescence (IF) analysis were performed to assess FXR levels in the lung and heart tissues of MCT-induced PAH and RHF rats. In normal rats, low FXR levels were detected in the heart, and nearly no FXR was expressed in rat lungs. However, FXR expression was significantly elevated in PAH and RHF rat lungs but reduced in PAH and RHF rat right ventricular (RV) tissues. FXR expression was reduced only in RHF rat left ventricular (LV) tissues.ConclusionsThe differential expression of FXR in MCT-induced PAH lungs and heart tissues in parallel with PAH pathophysiological processes suggests that FXR contributes to PAH.

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