Identification of an up-regulated anti-apoptotic network in the internal thoracic artery

Krane, Markus; Dummler, Sara; Dreßen, Martina; Hauner, Hans; Hoffmann, Micha; Haller, Dirk; Heller, Katharina; Wildhirt, Stephen; Voss, Bernhard; Grammer, Joachim; Lahm, Harald; Lange, Rüdiger; Bauernschmitt, Robert

doi:10.1016/j.ijcard.2010.02.003

« Previous Next »International Journal of Cardiology
Volume 149, Issue 2 , Pages 221-226, 2 June 2011

Identification of an up-regulated anti-apoptotic network in the internal thoracic artery

Markus Krane
- German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany
- Corresponding authors. Krane is to be contacted at Tel.: +49 89 12184111; fax: +49 89 12184113. Dummler, Tel.: +49 89 12183505; fax: +49 89 12183513.
- These authors have equally contributed.
Sara Dummler
- German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany
- Corresponding authors. Krane is to be contacted at Tel.: +49 89 12184111; fax: +49 89 12184113. Dummler, Tel.: +49 89 12183505; fax: +49 89 12183513.
- These authors have equally contributed.
Martina Dreßen
- German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany
Hans Hauner
- Else-Kröner-Fresenius-Centre for Nutritional Medicine at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany
Micha Hoffmann
- Chair for Biofunctionality, ZIEL-Research Centre for Nutrition and Food Science at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany
Dirk Haller
- Chair for Biofunctionality, ZIEL-Research Centre for Nutrition and Food Science at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany
Katharina Heller
- Chair for Biofunctionality, ZIEL-Research Centre for Nutrition and Food Science at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany
Stephen Wildhirt
- German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany
Bernhard Voss
- German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany
Joachim Grammer
- German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany
Harald Lahm
- German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany
Rüdiger Lange
- German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany
Robert Bauernschmitt
- German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany

Received 18 August 2009; received in revised form 19 November 2009; accepted 3 February 2010. published online 08 March 2010.

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.

Keywords: Atherosclerosis, Intimal hyperplasia, Radial artery, Internal thoracic artery, Anti-apoptosis, Gene expression