Non-invasive gene-expression-based detection of well-developed collateral function in individuals with and without coronary artery disease

Meier, Pascal; Antonov, Janine; Zbinden, Rainer; Kuhn, Aléxandre; Zbinden, Stephan; Gloekler, Steffen; Delorenzi, Mauro; Jaggi, Rolf; Seiler, Christian (2009). Non-invasive gene-expression-based detection of well-developed collateral function in individuals with and without coronary artery disease. Heart, 95(11), pp. 900-8. London: BMJ Publishing Group 10.1136/hrt.2008.145383

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BACKGROUND: In patients with coronary artery disease (CAD), a well grown collateral circulation has been shown to be important. The aim of this prospective study using peripheral blood monocytes was to identify marker genes for an extensively grown coronary collateral circulation. METHODS: Collateral flow index (CFI) was obtained invasively by angioplasty pressure sensor guidewire in 160 individuals (110 patients with CAD, and 50 individuals without CAD). RNA was extracted from monocytes followed by microarray-based gene-expression analysis. 76 selected genes were analysed by real-time polymerase chain reaction (PCR). A receiver operating characteristics analysis based on differential gene expression was then performed to separate individuals with poor (CFI<0.21) and well-developed collaterals (CFI>or=0.21) Thereafter, the influence of the chemokine MCP-1 on the expression of six selected genes was tested by PCR. RESULTS: The expression of 203 genes significantly correlated with CFI (p = 0.000002-0.00267) in patients with CAD and 56 genes in individuals without CAD (p = 00079-0.0430). Biological pathway analysis revealed 76 of those genes belonging to four different pathways: angiogenesis, integrin-, platelet-derived growth factor-, and transforming growth factor beta-signalling. Three genes in each subgroup differentiated with high specificity among individuals with low and high CFI (>or=0.21). Two out of these genes showed pronounced differential expression between the two groups after cell stimulation with MCP-1. CONCLUSIONS: Genetic factors play a role in the formation and the preformation of the coronary collateral circulation. Gene expression analysis in peripheral blood monocytes can be used for non-invasive differentiation between individuals with poorly and with well grown collaterals. MCP-1 can influence the arteriogenic potential of monocytes.

Item Type: Journal Article (Original Article)
Division/Institute: ?? DCD5A442B9C7E17DE0405C82790C4DE2 ??
04 Faculty of Medicine > Pre-clinic Human Medicine > Department of Clinical Research (DCR) > Forschungsbereich Pathologie > Forschungsgruppe Molekularbiologie
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology
08 Faculty of Science > Institute of Computer Science (INF)
UniBE Contributor: Meier, Pascal; Antonov, Janine; Zbinden, Rainer; Kuhn, Adrian; Zbinden, Stephan; Glökler, Steffen; Jaggi, Rolf and Seiler, Christian
ISSN: 1355-6037
ISBN: 18728069
Publisher: BMJ Publishing Group
Language: English
Submitter: Factscience Import
Date Deposited: 04 Oct 2013 15:02
Last Modified: 04 May 2014 23:18
Publisher DOI: 10.1136/hrt.2008.145383
PubMed ID: 18728069
Web of Science ID: 000266105600009
URI: http://boris.unibe.ch/id/eprint/26956 (FactScience: 99211)

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