title: Conventional therapies fail to target inflammation and immune imbalance in subjects with stable coronary artery disease: a system-based approach.
abstract: OBJECTIVE
  Cardiovascular diseases are the leading cause of morbidity and mortality. In spite of improved pharmacological interventions, the clinical outcome or response to therapy is poorly linked with the reversal of signs and symptoms of the disease.
  
  
  RESULTS
  Keeping this in view, we evaluated the post-treatment effect of standard therapies on traditional risk factors as well as inflammatory markers in 116 non-diabetic subjects with stable CAD undergoing treatment with conventional drugs for >3 months (Group-II) and 50 normal healthy controls (Group-I). We employed a top-down approach through Microarray and bioinformatics analysis to evaluate the distinct molecular signatures that remain unresponsive to the current therapies employed in clinics. Despite potent effects of therapy on serum cholesterol and LDL-C, triglycerides, VLDL-C and inflammatory markers such as hsCRP, Ox-LDL, IL-18, TNF-α and IL-6 remained high in these subjects versus controls. Microarray analysis revealed that despite treatment 513 genes were differentially expressed that play important role in various biological processes such as, i.e. inflammation (CXCR4, CXCL2, PTGS2), immune imbalance (IL-8, IL-Iß, CCL3), and active atherosclerosis (DUSP-1, OSM, ATF3). A positive correlation between hsCRP, IL-18, IL-8, PTGS2 and IL-Iß genes points these as candidate genes and therapeutic targets.
  
  
  CONCLUSIONS
  Our results clearly demonstrate that standard therapies for treatment and prevention of CAD fail to protect these subjects from ongoing inflammation and immune imbalance. Using a systems-based approach we propose a list of "Core-Genes" as probable candidate genes for therapeutic targeting.
authors.affiliation: Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Kapoor
authors.affiliation: Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Dimple
authors.initials: D
authors.lastname: Trikha
authors.affiliation: Department of Cardiology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Vijayvergiya
authors.affiliation: Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaul
authors.affiliation: Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: veena447@gmail.com.
authors.forename: Veena
authors.initials: V
authors.lastname: Dhawan
mesh_terms: D000328:Adult; D000368:Aged; D019743:Chemokines, CXC / Q000378:metabolism; D019295:Computational Biology; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000276:immunology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D053683:Oncostatin M / Q000378:metabolism; D012372:ROC Curve; D012307:Risk Factors; D013598:Systems Theory
chemical_list: C499707:CXCL3 protein, human; C508606:CXCL8 protein, human; D019743:Chemokines, CXC; D016209:Interleukin-8; D008055:Lipids; C508351:OSM protein, human; D053683:Oncostatin M; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1
keywords: Coronary artery disease (CAD); Gene expression; Immune imbalance; Inflammation; Micro-array