title: Time course of mitosis and collateral growth following coronary microembolization in the porcine heart.
abstract: In ischaemic porcine myocardium, the growth of collateral vessels by angiogenesis is observed in clusters in the vicinity of focal necroses. Because mitosis of endothelial cells is a prerequisite for angiogenesis, the purpose of this study has been to evaluate the time course of mitosis as an indicator of vascular growth in a porcine model of coronary microembolization. Ischaemia was induced by injection of 25-microm microspheres in the left circumflex artery, followed by tissue collection from non-ischaemic and ischaemic areas of the same heart after 24, 72 or 168 h microembolization. Tissue was studied by histone H3 in-situ hybridization, PCNA/cyclin immunohistochemistry and electron microscopy. The number of blood vessels in ischaemic myocardium was compared with that in normal control tissue. Capillary growth started as early as 24 h after microembolization, as indicated by increasing numbers of proliferating, histone H3- and PCNA/cyclin-positive cells in the necrotic inflammatory foci of the ischaemic area. At 72 h and 168 h, the number of blood vessels was significantly higher in ischaemic than in normal myocardium, whereas at 168 h, mitosis of cells was, as in normal myocardium, a rare event. Coronary microembolization of porcine myocardium thus leads to an increased cellular proliferation rate between 24 h and less than 7 days after the onset of microembolization, followed by enhanced capillary growth. In-situ hybridization with histone H3 and PCNA/cyclin immunohistochemistry seem to be reliable markers for proliferation and vascular growth in non-cancerogenic tissue.
authors.affiliation: Max Planck Institute for Physiological and Clinical Research, Department of Experimental Cardiology, Benekestrasse 2, D-61231 Bad Nauheim, Germany. rzimmer@kerckhoff.mpg.de
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: M
authors.initials: M
authors.lastname: Arras
authors.forename: C
authors.initials: C
authors.lastname: Ullmann
authors.forename: R
authors.initials: R
authors.lastname: Strasser
authors.forename: S
authors.initials: S
authors.lastname: Sack
authors.forename: H
authors.initials: H
authors.lastname: Mollnau
authors.forename: J
authors.initials: J
authors.lastname: Schaper
authors.forename: W
authors.initials: W
authors.lastname: Schaper
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D004617:Embolism / Q000503:physiopathology*; D005069:Evaluation Studies as Topic; D015870:Gene Expression / Q000502:physiology; D006657:Histones / Q000032:analysis / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007421:Intestine, Small / Q000737:chemistry / Q000502:physiology; D008833:Microcirculation / Q000502:physiology; D008854:Microscopy, Electron; D008938:Mitosis / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016196:S Phase / Q000502:physiology; D013552:Swine; D013997:Time Factors
chemical_list: D006657:Histones; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger