Localization of Islet-1–Positive Cells in the Healthy and Infarcted Adult Murine Heart

  • Florian Weinberger
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (F.W., D.M., F.W.F., L.C., T.E.); the Department of Cardiovascular Surgery, TSI-Lab, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., X.H., S.S.); the Institute of Cellular and Integrative Physiology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg,...
  • Dennis Mehrkens
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (F.W., D.M., F.W.F., L.C., T.E.); the Department of Cardiovascular Surgery, TSI-Lab, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., X.H., S.S.); the Institute of Cellular and Integrative Physiology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg,...
  • Felix W. Friedrich
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (F.W., D.M., F.W.F., L.C., T.E.); the Department of Cardiovascular Surgery, TSI-Lab, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., X.H., S.S.); the Institute of Cellular and Integrative Physiology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg,...
  • Mandy Stubbendorff
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (F.W., D.M., F.W.F., L.C., T.E.); the Department of Cardiovascular Surgery, TSI-Lab, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., X.H., S.S.); the Institute of Cellular and Integrative Physiology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg,...
  • Xiaoqin Hua
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (F.W., D.M., F.W.F., L.C., T.E.); the Department of Cardiovascular Surgery, TSI-Lab, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., X.H., S.S.); the Institute of Cellular and Integrative Physiology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg,...
  • Jana Christina Müller
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (F.W., D.M., F.W.F., L.C., T.E.); the Department of Cardiovascular Surgery, TSI-Lab, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., X.H., S.S.); the Institute of Cellular and Integrative Physiology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg,...
  • Sonja Schrepfer
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (F.W., D.M., F.W.F., L.C., T.E.); the Department of Cardiovascular Surgery, TSI-Lab, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., X.H., S.S.); the Institute of Cellular and Integrative Physiology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg,...
  • Sylvia M. Evans
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (F.W., D.M., F.W.F., L.C., T.E.); the Department of Cardiovascular Surgery, TSI-Lab, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., X.H., S.S.); the Institute of Cellular and Integrative Physiology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg,...
  • Lucie Carrier
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (F.W., D.M., F.W.F., L.C., T.E.); the Department of Cardiovascular Surgery, TSI-Lab, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., X.H., S.S.); the Institute of Cellular and Integrative Physiology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg,...
  • Thomas Eschenhagen
    From the Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (F.W., D.M., F.W.F., L.C., T.E.); the Department of Cardiovascular Surgery, TSI-Lab, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (M.S., X.H., S.S.); the Institute of Cellular and Integrative Physiology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg,...

抄録

<jats:sec> <jats:title> <jats:underline>Rationale:</jats:underline> </jats:title> <jats:p> The transcription factor Islet-1 is a marker of cardiovascular progenitors during embryogenesis. The isolation of Islet-1–positive (Islet-1 <jats:sup>+</jats:sup> ) cells from early postnatal hearts suggested that Islet-1 also marks cardiac progenitors in adult life. </jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Objective:</jats:underline> </jats:title> <jats:p> We investigated the distribution and identity of Islet-1 <jats:sup>+</jats:sup> cells in adult murine heart and evaluated whether their number or distribution change with age or after myocardial infarction. </jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Methods and Results:</jats:underline> </jats:title> <jats:p> Distribution of Islet-1 <jats:sup>+</jats:sup> cells in adult heart was investigated using gene targeted mice with nuclear β-galactosidase inserted into the Islet-1 locus. nLacZ-positive cells were only present in 3 regions of the adult heart: clusters in the interatrial septum and around the pulmonary veins, scattered within the wall of the great vessels, and a strictly delimited cluster between the right atrium and superior vena cava. Islet-1 <jats:sup>+</jats:sup> cells in the first type of clusters coexpressed markers for parasympathetic neurons. Positive cells in the great arteries coexpressed smooth muscle actin and myosin heavy chain, indicating a smooth muscle cell identity. Very few Islet-1 <jats:sup>+</jats:sup> cells within the outflow tract expressed the cardiomyocyte marker α-actinin. Islet-1 <jats:sup>+</jats:sup> cells in the right atrium coexpressed the sinoatrial node pacemaker cell marker HCN4. Cell number and localization remained unchanged between 1 to 18 months of age. Consistently Islet-1 mRNA was detected in human sinoatrial node. Islet-1 <jats:sup>+</jats:sup> cells could not be detected in the infarct zone 2 to 28 days after myocardial infarction, aside from 10 questionable cells in 1/13 hearts. </jats:p> </jats:sec> <jats:sec> <jats:title> <jats:underline>Conclusions:</jats:underline> </jats:title> <jats:p> Our results identify Islet-1 as a novel marker of the adult sinoatrial node and do not provide evidence for Islet-1 <jats:sup>+</jats:sup> cells to serve as cardiac progenitors. </jats:p> </jats:sec>

収録刊行物

  • Circulation Research

    Circulation Research 110 (10), 1303-1310, 2012-05-11

    Ovid Technologies (Wolters Kluwer Health)

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