Identification of an up-regulated anti-apoptotic network in the internal thoracic artery.
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.
Krane
Markus
M
German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany. Electronic address: krane@dhm.mhn.de.
Dummler
Sara
S
German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany. Electronic address: dummler@dhm.mhn.de.
Dreßen
Martina
M
German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
Hauner
Hans
H
Else-Kröner-Fresenius-Centre for Nutritional Medicine at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany.
Hoffmann
Micha
M
Chair for Biofunctionality, ZIEL-Research Centre for Nutrition and Food Science at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany.
Haller
Dirk
D
Chair for Biofunctionality, ZIEL-Research Centre for Nutrition and Food Science at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany.
Heller
Katharina
K
Chair for Biofunctionality, ZIEL-Research Centre for Nutrition and Food Science at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany.
Wildhirt
Stephen
S
German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
Voss
Bernhard
B
German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
Grammer
Joachim
J
German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
Lahm
Harald
H
German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
Lange
Rüdiger
R
German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
Bauernschmitt
Robert
R
German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany.
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