title: Myocardial production and release of MCP-1 and SDF-1 following myocardial infarction: differences between mice and man.
abstract: BACKGROUND
  Stem cell homing to the heart is mediated by the release of chemo-attractant cytokines. Stromal derived factor -1 alpha (SDF-1a) and monocyte chemotactic factor 1(MCP-1) are detectable in peripheral blood after myocardial infarction (MI). It remains unknown if they are produced by, and released from, the heart in order to attract stem cells to repair the damaged myocardium.
  
  
  METHODS
  Murine hearts were studied for expression of MCP-1 and SDF-1a at day 3 and day 28 following myocardial infarction to determine whether production is increased following MI. In addition, we studied the coronary artery and coronary sinus (venous) blood from patients with normal coronary arteries, stable coronary artery disease (CAD), unstable angina and MI to determine whether these cytokines are released from the heart into the systemic circulation following MI.
  
  
  RESULTS
  Both MCP-1 and SDF-1a are constitutively produced and released by the heart. MCP-1 mRNA is upregulated following murine experimental MI, but SDF-1a is suppressed. There is less release of SDF-1a into the systemic circulation in patients with all stages of CAD including MI, mimicking the animal model. However MCP-1 release from the human heart following MI is also suppressed, which is the exact opposite of the animal model.
  
  
  CONCLUSIONS
  SDF-1a and MCP-1 release from the human heart are suppressed following MI. In the case of SDF-1a, the animal model appropriately reflects the human situation. However, for MCP-1 the animal model is the exact opposite of the human condition. Human observational studies like this one are paramount in guiding translation from experimental studies to clinical trials.
authors.affiliation: Department of Medicine, Division of Cardiology, University of California San Francisco, USA. aboyle@medicine.ucsf.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Boyle
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
authors.forename: Henry
authors.initials: H
authors.lastname: Shih
authors.forename: Joy
authors.initials: J
authors.lastname: Hwang
authors.forename: Jianqin
authors.initials: J
authors.lastname: Ye
authors.forename: Rich
authors.initials: R
authors.lastname: Sievers
authors.forename: Daiwei
authors.initials: D
authors.lastname: Zheng
authors.forename: Jath
authors.initials: J
authors.lastname: Palasubramaniam
authors.forename: Dharshan
authors.initials: D
authors.lastname: Palasubramaniam
authors.forename: Connie
authors.initials: C
authors.lastname: Karschimkus
authors.forename: Robert
authors.initials: R
authors.lastname: Whitbourn
authors.forename: Alicia
authors.initials: A
authors.lastname: Jenkins
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wilson
mesh_terms: D000368:Aged; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D012333:RNA, Messenger