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

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⩾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 β-signalling. Three genes in each subgroup differentiated with high specificity among individuals with low and high CFI (⩾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.

[1]  W. F. M. Fulton,et al.  Arterial Anastomoses in the Coronary Circulation , 1963 .

[2]  W. F. Fulton,et al.  ARTERIAL ANASTOMOSES IN THE CORONARY CIRCULATION. I. ANATOMICAL FEATURES IN NORMAL AND DISEASED HEARTS DEMONSTRATED BY STEREOARTERIOGRAPHY. , 1963, Scottish medical journal.

[3]  B. De Bruyne,et al.  Experimental Basis of Determining Maximum Coronary, Myocardial, and Collateral Blood Flow by Pressure Measurements for Assessing Functional Stenosis Severity Before and After Percutaneous Transluminal Coronary Angioplasty , 1993, Circulation.

[4]  B Meier,et al.  Coronary collateral quantitation in patients with coronary artery disease using intravascular flow velocity or pressure measurements. , 1998, Journal of the American College of Cardiology.

[5]  F. Eberli,et al.  Frequency distribution of collateral flow and factors influencing collateral channel development. Functional collateral channel measurement in 450 patients with coronary artery disease. , 2001, Journal of the American College of Cardiology.

[6]  Subir Ghosh,et al.  Nonparametric Analysis of Longitudinal Data in Factorial Experiments , 2003, Technometrics.

[7]  S. Windecker,et al.  Is There Functional Collateral Flow During Vascular Occlusion in Angiographically Normal Coronary Arteries? , 2003, Circulation.

[8]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

[9]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[10]  M. Voskuil,et al.  CD44 Regulates Arteriogenesis in Mice and Is Differentially Expressed in Patients With Poor and Good Collateralization , 2004, Circulation.

[11]  S. Grundmann,et al.  Differential effects of MCP-1 and leptin on collateral flow and arteriogenesis. , 2004, Cardiovascular research.

[12]  M. Burnett,et al.  Temporal patterns of gene expression after acute hindlimb ischemia in mice: insights into the genomic program for collateral vessel development. , 2004, Journal of the American College of Cardiology.

[13]  Benjamin M. Bolstad,et al.  affy - analysis of Affymetrix GeneChip data at the probe level , 2004, Bioinform..

[14]  M. West,et al.  Gene Expression Phenotypes of Atherosclerosis , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[15]  Gordon K Smyth,et al.  Statistical Applications in Genetics and Molecular Biology Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments , 2011 .

[16]  P. M. Hwang,et al.  Circulating transcriptome reveals markers of atherosclerosis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. West,et al.  Molecular evidence for arterial repair in atherosclerosis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[18]  S. Windecker,et al.  Safety and efficacy of subcutaneous-only granulocyte-macrophage colony-stimulating factor for collateral growth promotion in patients with coronary artery disease. , 2005, Journal of the American College of Cardiology.

[19]  U. Ikeda,et al.  Gene expression profiling of human atrial myocardium with atrial fibrillation by DNA microarray analysis. , 2005, International journal of cardiology.

[20]  W. Schaper,et al.  Arteriogenesis versus angiogenesis: similarities and differences , 2006, Journal of cellular and molecular medicine.

[21]  Fei Xiong,et al.  Transcriptional Profiling in Coronary Artery Disease: Indications for Novel Markers of Coronary Collateralization , 2006, Circulation.

[22]  Thomas Schmitz-Rixen,et al.  The Range of Adaptation by Collateral Vessels After Femoral Artery Occlusion , 2006, Circulation research.

[23]  S. Windecker,et al.  Collateral-flow measurements in humans by myocardial contrast echocardiography: validation of coronary pressure-derived collateral-flow assessment. , 2006, European heart journal.

[24]  D. Walther,et al.  Gene Expression Profiles and B-Type Natriuretic Peptide Elevation in Heart Transplantation: More Than a Hemodynamic Marker , 2006, Circulation.