title: Coronary Microembolization Induces Cardiomyocyte Apoptosis Through the LOX-1-Dependent Endoplasmic Reticulum Stress Pathway Involving JNK/P38 MAPK.
abstract: BACKGROUND
  Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a membrane protein associated with apoptosis. Endoplasmic reticulum (ER) stress-induced apoptosis has been determined in several cardiovascular diseases. Mitogen-activated protein kinase (MAPK) signalling is involved in apoptosis. The aim of this study was to investigate whether LOX-1, ER stress, and MAPKs play a role in cardiomyocyte apoptosis after coronary microembolization (CME) and the exact mechanisms involved.
  
  
  METHODS
  Thirty swine were randomized into the following groups (n = 5 per group): sham, CME, CME + LOX-1 small-interfering RNA (siRNA), CME + control siRNA, CME + JNK inhibitor, and CME + p38 inhibitor. The CME model was established by injecting microspheres into the left anterior descending (LAD) artery, whereas swine in the sham group received normal saline instead. Twelve hours after the sham operation or CME, cardiac function, serum c-troponin I level, microinfarcts, and apoptotic index were determined. Relative expression levels of LOX-1, ER stress markers (glucose-regulated protein 78 [GRP 78], C/EBP homologous protein [CHOP], and cleaved caspase-12), cleaved caspase-3, c-Jun NH2-terminal protein kinases (JNK), p38, and extracellular signal-related protein kinases (ERK1/2) were measured.
  
  
  RESULTS
  CME induced cardiac dysfunction, microinfarction, increased serum c-troponin I levels, and cardiomyocyte apoptosis. Additionally, the expression of LOX-1, ER stress markers, and cleaved caspase-3, and the phosphorylation of JNK, p38, and ERK1/2 were all enhanced. LOX-1 siRNA inhibited these effects except the phosphorylation of ERK1/2. Pretreatment with a JNK inhibitor or a p38 inhibitor attenuated the expression of ER stress markers and apoptosis.
  
  
  CONCLUSIONS
  Our results indicated that CME induced cardiomyocyte apoptosis through the LOX-1-dependent ER stress pathway, in which the phosphorylation of JNK and p38 were involved. This might provide a new approach for the prevention and treatment of CME.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Minzu Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Yang-Chun
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Wuhan Asia Heart Hospital, Wuhan, Hubei, China.
authors.forename: Jiang-You
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Su
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Zhong-Li
authors.initials: ZL
authors.lastname: Tang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. Electronic address: drlilang@163.com.
authors.forename: Lang
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D004617:Embolism / Q000150:complications / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D006334:Heart Function Tests; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008863:Microspheres; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D013552:Swine; D019209:Troponin C / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D019209:Troponin C; C099252:oxidized low density lipoprotein; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases