title: The transient receptor potential vanilloid 2 cation channel is abundant in macrophages accumulating at the peri-infarct zone and may enhance their migration capacity towards injured cardiomyocytes following myocardial infarction.
abstract: OBJECTIVE
  A novel family of transient receptor potential (TRP) channels, that may hold a role in calcium homeostasis, has recently been described. By employing a GeneChip array analysis we have demonstrated a clear and specific upregulation of the TRP vanilloid 2 (TRPV2) mRNA in the left ventricles (LV) 3-5 days post-acute myocardial infarction (MI) compared to sham-operated controls, both in rats and in mice. We sought to characterize the cardiac cellular subpopulations in which TRPV2 is overexpressed upon acute MI.
  
  
  METHODS
  Lewis rats underwent an acute MI by ligation of the left anterior descending artery or chest opening only (sham). The animals were terminated at various time points and an immunohistochemical (IHC) and immunofluorescent (IFC) staining of the LV sections as well as a flow cytometry analysis of LV-derived cells were carried out, using anti-TRPV2 and anti-monocyte/macrophage antibodies. Rat alveolar macrophage cells, NR8383, transiently transfected with TRPV2 siRNA were allowed to migrate towards hypoxic conditioned media of the rat cardiac myoblast line H9C2 using a trans-well migration assay. The macrophage cells migrating to the bottom side of the inserts were counted.
  
  
  RESULTS
  The IHC and IFC staining as well as the flow cytometry data demonstrated a substantial expression of TRPV2 in infiltrating macrophages in the peri-infarct region 3-5 days post-acute MI. The in vitro migration assay data demonstrated that following inhibition of the TRPV2 channel, the number of migrating macrophages towards conditioned medium of hypoxic cardiomyocytes was significantly reduced.
  
  
  CONCLUSIONS
  TRPV2 is highly expressed on the peri-infarct infiltrating macrophages and may play an important role in post-MI phagocytosis. Better characterization of this channel may pave the way for identifying a new target for modulating the dramatic post-MI immune reactions.
authors.affiliation: Laboratory of Cardiovascular Research, Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Entin-Meer
authors.affiliation: Laboratory of Cardiovascular Research, Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Ran
authors.initials: R
authors.lastname: Levy
authors.affiliation: Laboratory of Cardiovascular Research, Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Pavel
authors.initials: P
authors.lastname: Goryainov
authors.affiliation: Neufeld Cardiac Research Institute, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Natalie
authors.initials: N
authors.lastname: Landa
authors.affiliation: Department of Pathology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.affiliation: Department of Pathology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Camila
authors.initials: C
authors.lastname: Avivi
authors.affiliation: Laboratory of Cardiovascular Research, Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Semo
authors.affiliation: Laboratory of Cardiovascular Research, Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: Gad
authors.initials: G
authors.lastname: Keren
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D015870:Gene Expression; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000502:physiology*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D011917:Rats, Inbred Lew; D050916:TRPV Cation Channels / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D039481:CD11b Antigen; D050916:TRPV Cation Channels; C476722:Trpv2 protein, rat; D007334:Insulin-Like Growth Factor I