title: Characterization of a novel endothelial biosensor assay reveals increased cumulative serum inflammatory potential in stabilized coronary artery disease patients.
abstract: BACKGROUND
  Vascular disease is promoted by systemic inflammation that can arise from sites distal to the affected vessels. We sought to characterize the net inflammatory potential of serum from patients with coronary artery disease (CAD) using cultured endothelial cells as a cumulative biosensor.
  
  
  RESULTS
  Serum samples from CAD patients (N = 45) and healthy control subjects (N = 48) were incubated with primary human coronary artery endothelial cells at a 1:10 dilution for 4 h, followed by isolation of the cellular RNA. Alteration of inflammation-responsive elements (adhesion molecules and cytokines) was assessed by gene expression. Specific indicators included intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and interleukin-8 (IL-8). Additionally, the cytokine levels in serum samples from all subjects were quantified. Serum from CAD subjects induced greater endothelial ICAM-1, VCAM-1, and IL-8 expression compared to healthy control serum (p < 0.001 for each analysis). The three indicators of inflammatory potential (ICAM-1, VCAM-1, and IL-8 mRNA) trended independently of each other and also of serum inflammatory biomarkers. IL-8 expression correlated negatively with serum HDL levels but positively correlated with VLDL, plasminogen activator inhibitor-1 and C-reactive protein. Interestingly, serum levels of cytokines in CAD patients were not statistically different from healthy control subjects. A year of follow-up in a sub-group of CAD subjects revealed relatively stable measures.
  
  
  CONCLUSIONS
  As yet unidentified circulating factors in the serum of CAD patients appear to activate endothelial cells, leading to upregulation of adhesion molecules and chemokines. This cumulative assay performed well in terms of discriminating patients with CAD compared to healthy subjects, with greater range and specificity than specific inflammatory markers.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA. HCung01@salud.unm.edu.
authors.forename: Heidi
authors.initials: H
authors.lastname: Cung
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA. MJAragon@salud.unm.edu.
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Aragon
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA. KZychowski@salud.unm.edu.
authors.forename: Katherine
authors.initials: K
authors.lastname: Zychowski
authors.affiliation: Department of Pharmacy Practice and Administrative Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA. JAnderson@salud.unm.edu.
authors.forename: Joe R
authors.initials: JR
authors.lastname: Anderson
authors.affiliation: Department of Pharmacy Practice and Administrative Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA. JNawarskas@salud.unm.edu.
authors.forename: James
authors.initials: J
authors.lastname: Nawarskas
authors.affiliation: Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA. CRoldan@salud.unm.edu.
authors.forename: Carlos
authors.initials: C
authors.lastname: Roldan
authors.affiliation: Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA. ASood@salud.unm.edu.
authors.forename: Akshay
authors.initials: A
authors.lastname: Sood
authors.affiliation: Department of Biostatistics, School of Medicine, University of New Mexico, Albuquerque, NM, USA. CQualls@salud.unm.edu.
authors.forename: Clifford
authors.initials: C
authors.lastname: Qualls
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA. mcampen@unm.edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Campen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001681:Biological Assay / Q000379:methods*; D015374:Biosensing Techniques / Q000379:methods*; D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology; D003710:Demography; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D016014:Linear Models; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis; D012727:Sex Characteristics; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1