title: Hyperhomocysteinemia inhibited cardiac stem cell homing into the peri-infarcted area post myocardial infarction in rats.
abstract: BACKGROUND
  Hyperhomocysteinemia (HHcy) has been reported as an independent risk factor for coronary artery disease; however it is not clear regarding the action of HHcy on the homing of cardiac stem cells (CSCs) to the damaged myocardium and the consequent CSCs-mediated cardiac repair post myocardial infarction.
  
  
  METHODS
  Sprague-Dawley (SD) rats were divided into 4 groups. HHcy was induced in the rats by a 6-week high-methionine diet. Rat heart MI model was developed by left coronary artery ligation. Immunofluorescence was used to examine the CSCs migration in vivo via injecting BrdU-labeled CSCs into AV-groove followed by a coronary ligation. Immunohistochemistry, western blot and ELISA analysis were carried out to detect the expression of stem cell factor (SCF) protein, and RT-PCR was conducted for the expression of SCF mRNA.
  
  
  RESULTS
  On day 5 of MI model creation, accumulation of CSCs was significantly increased in the peri-infarcted area by the non-hyperhomocysteinemic rats, which led to an improvement of cardiac function at 3 weeks after MI. however, the accumulation of CSCs was markedly decreased by the hyperhomocysteinemic rats followed with the decline of cardiac function. SCF expression was also significantly decreased in the peri-infarcted area by the hyperhomocysteinemic rats compared to the non-hyperhomocysteinemic rats. The experiments in vitro confirmed that homocysteine (Hcy) decreased SCF expression via inhibition of TNF-α-induced activity of NF-κB, further reduced the migration of CSCs.
  
  
  CONCLUSIONS
  It demonstrated that hyperhomocysteinemia may significantly contribute to restrain CSCs-mediated cardiac repair by reducing SCF-induced homing of CSCs.
authors.affiliation: Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wan
authors.forename: Yunte
authors.initials: Y
authors.lastname: Deng
authors.forename: Junli
authors.initials: J
authors.lastname: Guo
authors.forename: Guixiang
authors.initials: G
authors.lastname: Xiao
authors.forename: Dong
authors.initials: D
authors.lastname: Kuang
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Duan
authors.forename: Guoping
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006710:Homocysteine / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D008715:Methionine / Q000008:administration & dosage; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: D019089:Stem Cell Factor; D006710:Homocysteine; D008715:Methionine