title: Identification of an up-regulated anti-apoptotic network in the internal thoracic artery.
abstract: BACKGROUND
  The radial artery (RA) is known as an atherosclerosis-prone vessel in contrast to the atherosclerosis-resistant internal thoracic artery (ITA). The purpose of the present study was to compare the gene expression profile of these arteries from the same patient in order to identify genes involved in atherogenesis or intimal hyperplasia.
  
  
  METHODS
  Paired specimens of RA and ITA (n=6) were analyzed by histomorphometry and whole genome microarray. The microarray data underwent pathway analysis to identify biological networks. Laser microdissection (LMD) was used to identify the cellular expression of candidate genes in the intimal or medial layer of the ITA and RA.
  
  
  RESULTS
  Histomorphometric analyses revealed a significantly higher degree of intimal hyperplasia in the RA compared to the ITA. 552 genes were differentially expressed in the ITA and RA. qRT-PCR confirmed a significant up-regulation of six anti-apoptotic genes. p21 (11.8-fold, p=0.011), CCL2 (5.4-fold, p=0.034), SOCS3 (7.2-fold, p=0.002), IER3 (4.1-fold, p=0.048), MCL-1 (2.6-fold, p=0.025) and IL-6 (17.8-fold, p=0.046) were up-regulated in the ITA. LMD confirmed that cells of the intimal layer of the ITA consistently expressed higher levels of all six candidate genes than those of the RA.
  
  
  CONCLUSIONS
  Microarray analysis and qRT-PCR identified significantly up-regulated genes in the ITA involved in an anti-apoptotic network. LMD revealed a higher expression of all anti-apoptotic genes in the intimal area of the ITA. These genes may play an important role in protecting the intima of the ITA from developing hyperplasia and atherosclerosis.
authors.affiliation: German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany. Electronic address: krane@dhm.mhn.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Krane
authors.affiliation: German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany. Electronic address: dummler@dhm.mhn.de.
authors.forename: Sara
authors.initials: S
authors.lastname: Dummler
authors.affiliation: German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Dreßen
authors.affiliation: Else-Kröner-Fresenius-Centre for Nutritional Medicine at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.affiliation: Chair for Biofunctionality, ZIEL-Research Centre for Nutrition and Food Science at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany.
authors.forename: Micha
authors.initials: M
authors.lastname: Hoffmann
authors.affiliation: Chair for Biofunctionality, ZIEL-Research Centre for Nutrition and Food Science at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Haller
authors.affiliation: Chair for Biofunctionality, ZIEL-Research Centre for Nutrition and Food Science at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Heller
authors.affiliation: German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
authors.forename: Stephen
authors.initials: S
authors.lastname: Wildhirt
authors.affiliation: German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Voss
authors.affiliation: German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Grammer
authors.affiliation: German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Lahm
authors.affiliation: German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Lange
authors.affiliation: German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Bauernschmitt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics* / Q000502:physiology; D001026:Coronary Artery Bypass / Q000379:methods; D053263:Gene Regulatory Networks / Q000502:physiology*; D006801:Humans; D008323:Mammary Arteries / Q000502:physiology*; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D015854:Up-Regulation / Q000235:genetics* / Q000502:physiology