title: Endothelial plasticity drives arterial remodeling within the endocardium after myocardial infarction.
abstract: BACKGROUND
  Revascularization of injured, ischemic, and regenerating organs is essential to restore organ function. In the postinfarct heart, however, the mechanisms underlying the formation of new coronary arteries are poorly understood.
  
  
  OBJECTIVE
  To study vascular remodeling of coronary arteries after infarction.
  
  
  RESULTS
  We performed permanent left coronary ligation on Connexin40-GFP mice expressing green fluorescent protein (GFP) in endothelial cells of coronary arteries but not veins, capillaries, or endocardium. GFP(+) endothelial foci were identified within the endocardium in the infarct zone. These previously undescribed structures, termed endocardial flowers, have a distinct endothelial phenotype (Cx40(+), VEGFR2(+), and endoglin(-)) to the surrounding endocardium (Cx40(-), VEGFR2(-), and endoglin(+)). Endocardial flowers are contiguous with coronary vessels and associated with subendocardial smooth muscle cell accumulation. Genetic lineage tracing reveals extensive endothelial plasticity in the postinfarct heart, showing that endocardial flowers develop by arteriogenesis of Cx40(-) cells and by outgrowth of pre-existing coronary arteries. Finally, endocardial flowers exhibit angiogenic features, including early VEGFR2 expression and active proliferation of adjacent endocardial and smooth muscle cells.
  
  
  CONCLUSIONS
  Arterial endothelial foci within the endocardium reveal extensive endothelial cell plasticity in the infarct zone and identify the endocardium as a site of endogenous arteriogenesis and source of endothelial cells to promote vascularization in regenerative strategies.
authors.affiliation: From Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille, France (L.M., R.S., R.G.K.); and PHYMEDEXP, Physiologie et Médecine Expérimentale Cœur et Muscles, INSERM U1046, CNRS UMR 9214, Université de Montpellier, CHU Arnaud de Villeneuve, Montpellier, France (J.T., P.B, S.R.). lucile.miquerol@univ-amu.fr.
authors.forename: Lucile
authors.initials: L
authors.lastname: Miquerol
authors.affiliation: From Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille, France (L.M., R.S., R.G.K.); and PHYMEDEXP, Physiologie et Médecine Expérimentale Cœur et Muscles, INSERM U1046, CNRS UMR 9214, Université de Montpellier, CHU Arnaud de Villeneuve, Montpellier, France (J.T., P.B, S.R.).
authors.forename: Jérome
authors.initials: J
authors.lastname: Thireau
authors.affiliation: From Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille, France (L.M., R.S., R.G.K.); and PHYMEDEXP, Physiologie et Médecine Expérimentale Cœur et Muscles, INSERM U1046, CNRS UMR 9214, Université de Montpellier, CHU Arnaud de Villeneuve, Montpellier, France (J.T., P.B, S.R.).
authors.forename: Patrice
authors.initials: P
authors.lastname: Bideaux
authors.affiliation: From Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille, France (L.M., R.S., R.G.K.); and PHYMEDEXP, Physiologie et Médecine Expérimentale Cœur et Muscles, INSERM U1046, CNRS UMR 9214, Université de Montpellier, CHU Arnaud de Villeneuve, Montpellier, France (J.T., P.B, S.R.).
authors.forename: Rachel
authors.initials: R
authors.lastname: Sturny
authors.affiliation: From Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille, France (L.M., R.S., R.G.K.); and PHYMEDEXP, Physiologie et Médecine Expérimentale Cœur et Muscles, INSERM U1046, CNRS UMR 9214, Université de Montpellier, CHU Arnaud de Villeneuve, Montpellier, France (J.T., P.B, S.R.).
authors.forename: Sylvain
authors.initials: S
authors.lastname: Richard
authors.affiliation: From Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille, France (L.M., R.S., R.G.K.); and PHYMEDEXP, Physiologie et Médecine Expérimentale Cœur et Muscles, INSERM U1046, CNRS UMR 9214, Université de Montpellier, CHU Arnaud de Villeneuve, Montpellier, France (J.T., P.B, S.R.).
authors.forename: Robert G
authors.initials: RG
authors.lastname: Kelly
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004699:Endocardium / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009203:Myocardial Infarction / Q000503:physiopathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D000071063:Endoglin; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2; D000097003:Gap Junction alpha-5 Protein; C502004:Eng protein, mouse; C000592875:Kdr protein, mouse
keywords: blood supply; coronary vessels; endocardium; myocardial infarction; vascular remodeling