title: Farnesoid-X-receptor expression in monocrotaline-induced pulmonary arterial hypertension and right heart failure.
abstract: OBJECTIVE
  The 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.
  
  
  RESULTS
  Hemodynamic 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.
  
  
  CONCLUSIONS
  The differential expression of FXR in MCT-induced PAH lungs and heart tissues in parallel with PAH pathophysiological processes suggests that FXR contributes to PAH.
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China; Department of Rheumatology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325015, China.
authors.forename: Lusi
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China. Electronic address: susanzuo@hotmail.com.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zuo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D006333:Heart Failure / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D066253:Vascular Remodeling; D020257:Ventricular Remodeling; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D016686:Monocrotaline; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated
keywords: FXR; Heart; Lung; PAH; RHF