Markus Krane1, Sara Dummler2, Martina Dreßen3, Hans Hauner4, Micha Hoffmann5, Dirk Haller5, Katharina Heller5, Stephen Wildhirt3, Bernhard Voss3, Joachim Grammer3, Harald Lahm3, Rüdiger Lange3, Robert Bauernschmitt3. 1. German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany. Electronic address: krane@dhm.mhn.de. 2. German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany. Electronic address: dummler@dhm.mhn.de. 3. German Heart Centre Munich at the Technische Universität München, Department of Cardiovascular Surgery, Lazarettstrasse 36, 80636 Munich, Germany. 4. Else-Kröner-Fresenius-Centre for Nutritional Medicine at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany. 5. Chair for Biofunctionality, ZIEL-Research Centre for Nutrition and Food Science at the Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising-Weihenstephan, Germany.
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.
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.