Genetic Fate Mapping Defines the Vascular Potential of Endocardial Cells in the Adult Heart.

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  • Additional Information
    • Source:
      Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0047103 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4571 (Electronic) Linking ISSN: 00097330 NLM ISO Abbreviation: Circ Res
    • Publication Information:
      Publication: Baltimore, MD : Lippincott Williams & Wilkins
      Original Publication: Baltimore, Md. Grune & Stratton.
    • Subject Terms:
      Neovascularization, Physiologic*; Cell Lineage/*genetics ; Endocardium/*cytology ; Endothelium, Vascular/*cytology ; Stem Cell Transplantation/*methods; Animals ; Aortic Valve Stenosis/metabolism ; Aortic Valve Stenosis/pathology ; Aortic Valve Stenosis/therapy ; Cell Line ; Cell Transdifferentiation ; Coronary Vessels/cytology ; Coronary Vessels/metabolism ; Endocardium/metabolism ; Endothelium, Vascular/metabolism ; Humans ; Mice ; Myocardial Reperfusion Injury/metabolism ; Myocardial Reperfusion Injury/pathology ; Myocardial Reperfusion Injury/therapy ; Receptors, Atrial Natriuretic Factor/genetics ; Receptors, Atrial Natriuretic Factor/metabolism
    • Abstract:
      Rationale: Endocardium is the major source of coronary endothelial cells (ECs) in the fetal and neonatal hearts. It remains unclear whether endocardium in the adult stage is also the main origin of neovascularization after cardiac injury.
      Objective: To define the vascular potential of adult endocardium in homeostasis and after cardiac injuries by fate-mapping studies.
      Methods and Results: We generate an inducible adult endocardial Cre line ( Npr3 [natriuretic peptide receptor C]- CreER ) and show that Npr3-CreER efficiently and specifically labels endocardial cells but not coronary blood vessels in the adult heart. The adult endocardial cells do not contribute to any vascular ECs during cardiac homeostasis. To examine the formation of blood vessels from endocardium after injury, we generate 4 cardiac injury models with Npr3-CreER mice: myocardial infarction, myocardial ischemia-reperfusion, cryoinjury, and transverse aortic constriction. Lineage tracing experiments show that adult endocardium minimally contributes to coronary ECs after myocardial infarction. In the myocardial ischemia-reperfusion, cryoinjury, or transverse aortic constriction models, adult endocardial cells do not give rise to any vascular ECs, and they remain on the inner surface of myocardium that connects with lumen circulation. In the myocardial infarction model, very few endocardial cells are trapped in the infarct zone of myocardium shortly after ligation of coronary artery, indicating the involvement of endocardial entrapment during blood vessels formation. When these adult endocardial cells are relocated and trapped in the infarcted myocardium by transplantation or myocardial constriction model, very few endocardial cells survive and gain vascular EC properties, and their contribution to neovascularization in the injured myocardium remains minimal.
      Conclusions: Unlike its fetal or neonatal counterpart, adult endocardium naturally generates minimal, if any, coronary arteries or vascular ECs during cardiac homeostasis or after injuries.
      (© 2018 American Heart Association, Inc.)
    • Comments:
      Comment in: Circ Res. 2018 Mar 30;122(7):913-915. (PMID: 29599272)
    • Contributed Indexing:
      Keywords: cardiovascular disease; endocardium; ligation; mice; myocardium
    • Accession Number:
      EC 4.6.1.2 (Receptors, Atrial Natriuretic Factor)
      EC 4.6.1.2 (atrial natriuretic factor receptor C)
    • Publication Date:
      Date Created: 20180128 Date Completed: 20190809 Latest Revision: 20190809
    • Publication Date:
      20221213
    • Accession Number:
      10.1161/CIRCRESAHA.117.312354
    • Accession Number:
      29374073