Esenting each pathway. Thus integrating the purchase 298690-60-5 transcriptional changes which lead to differential expression of biomarkers and pathophysiology are needed to identify the best discerning molecular biomarkers. One of the most important aspects of translational research is the need to discover novel cardiovascular disease biomarkers for early detection of the pathogenesis, inform prognosis, guide therapy and monitor the disease progression. Despite several expectations from `omics technologies, elucidation of accurate and discriminating disease biomarkers for the clinical management still remains a challenge. Many 125-65-5 web studies have focused on using microarray and proteomics technologies for novel biomarker discovery. However, compared with massive knowledge about transcriptome/proteome, we have surprisingly little knowledge about regulatory mechanisms under-lying the biomarker diversity. To analyze the transcriptional regulatory programs, gene expression, proteomics, and integrative computational approaches that integrate regulatory sequence data are needed. So far many approaches have been developed in lower organisms like yeast to correlate between the presence of cisregulatory motifs and expression values [1,2]. On the other hand, such important analyses in 15900046 higher organisms like humans are just starting [3,4]. In this study we used transcription factor profiles, gene expression and proteomic expression data in combination with bioinformatics analysis to identify the core transcription factors which might regulate several interactive pathways associated with coronary artery disease (CAD). In our approach, we selected candidate biomarkers representatives of CAD associated pathways whose promoter regions were analyzed. Gene expression studies were carried to identify the expression levels of the transcription factors (TFs) which regulate the biomarkers and have correlated them with proteomic expression of biomarkers. Using this approach we have dissected a core set of transcriptional regulatory program which might give a better understanding of theTranscriptional Regulation Coronary Artery Diseaseassociation of differential expression of biomarkers/pathways with CAD.Institute ethics committee [23]. All participants gave their written informed consent to participate in the study.Methods Selection of BiomarkersGuided by recent reviews and research articles on biomarkers in cardiovascular diseases, a list of 31 known biomarkers were compiled from 7 different pathways shown to be highly associated with CAD. Biomarker selection was based on the association of individual biomarkers to CAD and their ability for risk prediction. Inflammation [5?2] and coagulation are the two major pathways known to be associated with CAD and therefore majority of biomarkers were selected from these pathways (inflammation: Interleukin 6 (IL6), Interleukin 8 (IL8), Interleukin 10 (IL10), Interleukin 12A (IL12A) [12], Interleukin 12B (IL12B) [12], Interleukin 18 (IL18), Monocyte chemoattractant protein-1 (MCP1 or CCL2), High sensitive C reactive protein (CRP), Interferon gamma (IFNG), Matrix metalloprotease-9 (MMP9) and secretary Phospholipase A2 (sPLA2 or PLA2G2A) and Gamma-glutamyltransferase 5 (GGT5) [7], Coagulation [8?3]: Factor VII, Fibrinogen alpha, beta, gamma, Prothrombin, Plasminogen activator inhibitor-1, Plasminogen (PLAT), Tissue factor [14], von Willebrand Factor, Platelet derived growth factor (PDGF) [15]. The other biomarkers selected were from pathways like.Esenting each pathway. Thus integrating the transcriptional changes which lead to differential expression of biomarkers and pathophysiology are needed to identify the best discerning molecular biomarkers. One of the most important aspects of translational research is the need to discover novel cardiovascular disease biomarkers for early detection of the pathogenesis, inform prognosis, guide therapy and monitor the disease progression. Despite several expectations from `omics technologies, elucidation of accurate and discriminating disease biomarkers for the clinical management still remains a challenge. Many studies have focused on using microarray and proteomics technologies for novel biomarker discovery. However, compared with massive knowledge about transcriptome/proteome, we have surprisingly little knowledge about regulatory mechanisms under-lying the biomarker diversity. To analyze the transcriptional regulatory programs, gene expression, proteomics, and integrative computational approaches that integrate regulatory sequence data are needed. So far many approaches have been developed in lower organisms like yeast to correlate between the presence of cisregulatory motifs and expression values [1,2]. On the other hand, such important analyses in 15900046 higher organisms like humans are just starting [3,4]. In this study we used transcription factor profiles, gene expression and proteomic expression data in combination with bioinformatics analysis to identify the core transcription factors which might regulate several interactive pathways associated with coronary artery disease (CAD). In our approach, we selected candidate biomarkers representatives of CAD associated pathways whose promoter regions were analyzed. Gene expression studies were carried to identify the expression levels of the transcription factors (TFs) which regulate the biomarkers and have correlated them with proteomic expression of biomarkers. Using this approach we have dissected a core set of transcriptional regulatory program which might give a better understanding of theTranscriptional Regulation Coronary Artery Diseaseassociation of differential expression of biomarkers/pathways with CAD.Institute ethics committee [23]. All participants gave their written informed consent to participate in the study.Methods Selection of BiomarkersGuided by recent reviews and research articles on biomarkers in cardiovascular diseases, a list of 31 known biomarkers were compiled from 7 different pathways shown to be highly associated with CAD. Biomarker selection was based on the association of individual biomarkers to CAD and their ability for risk prediction. Inflammation [5?2] and coagulation are the two major pathways known to be associated with CAD and therefore majority of biomarkers were selected from these pathways (inflammation: Interleukin 6 (IL6), Interleukin 8 (IL8), Interleukin 10 (IL10), Interleukin 12A (IL12A) [12], Interleukin 12B (IL12B) [12], Interleukin 18 (IL18), Monocyte chemoattractant protein-1 (MCP1 or CCL2), High sensitive C reactive protein (CRP), Interferon gamma (IFNG), Matrix metalloprotease-9 (MMP9) and secretary Phospholipase A2 (sPLA2 or PLA2G2A) and Gamma-glutamyltransferase 5 (GGT5) [7], Coagulation [8?3]: Factor VII, Fibrinogen alpha, beta, gamma, Prothrombin, Plasminogen activator inhibitor-1, Plasminogen (PLAT), Tissue factor [14], von Willebrand Factor, Platelet derived growth factor (PDGF) [15]. The other biomarkers selected were from pathways like.