title: LOX-1 promotes right ventricular hypertrophy in hypoxia-exposed rats.
abstract: OBJECTIVE
  Chronic hypoxia leads to right ventricular hypertrophy (RVH). RVH is believed to result from hypoxia-induced pulmonary hypertension. However, if hypoxia impacts RVH directly awaits clarification. Hypoxia triggers oxidative stress, and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediates reactive oxygen species (ROS) generation in different cells. Therefore, this study aims to explore whether LOX-1-mediated oxidative stress accounts for hypoxia-induced RVH.
  
  
  METHODS
  Rats developed RVH after 3weeks of hypoxia (10% O2). Immunofluorescence staining was performed to evaluate H9C2 cell hypertrophy induced by hypoxia (3% O2). Real-time PCR and Western-blot were performed to assess LOX-1, NADPH oxidases (NOX), collagen I/III, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) expression. DCFH-DA staining was performed to measure ROS generation.
  
  
  RESULTS
  Hypoxia induced RVH and cardiac fibrosis in rats, as indicated by enlarged cardiomyocytes and deposition of extracellular matrix. Interestingly, hypoxia treatment directly induced H9C2 cardiomyocyte hypertrophy, implying direct effects of hypoxia on cell hypertrophy. Rat and H9C2 hypertrophy model revealed that cell hypertrophy was accompanied by marked increase in LOX-1 expression. Knockdown of LOX-1 significantly ameliorated H9C2 cell hypertrophy. Mechanistically, hypoxia induced prominent oxidative stress in rat right ventricles and H9C2 cells, most likely as a result from increased expression of NOX2/4, contributing to RVH. Knockdown of LOX-1 significantly attenuated H9C2 cell oxidative stress, with a concomitant decrease in NOX2/4 expression.
  
  
  CONCLUSIONS
  LOX-1/NOX/ROS pathway could represent a novel mechanism underlying hypoxia-induced RVH. Therapeutic targeting of LOX-1 would be exploited to treat RVH owing to chronic hypoxia exposure.
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410078, China.
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410078, China; Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Luo
authors.affiliation: Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Zhao-Xin
authors.initials: ZX
authors.lastname: Qian
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Central South University, Changsha, Hunan 410078, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Central South University, Changsha, Hunan 410078, China. Electronic address: zzhang@csu.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Central South University, Changsha, Hunan 410078, China. Electronic address: huchangping@csu.edu.cn.
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D017380:Hypertrophy, Right Ventricular / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C495136:OLR1 protein, rat; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E
keywords: Cell hypertrophy; LOX-1; NADPH oxidase; ROS; RVH