title: Abacavir, didanosine and tenofovir do not induce inflammatory, apoptotic or oxidative stress genes in coronary endothelial cells.
abstract: BACKGROUND
  The use of abacavir and didanosine in HAART has been associated with an increased risk of myocardial infarction in HIV-infected patients. The aim of this study was to address the development of endothelial dysfunction in cultivated coronary artery endothelial cells (HCAECs) in response to abacavir, didanosine and tenofovir. We examined the impact of these drugs on the expression levels of the proinflammatory, oxidative stress and apoptosis regulating genes in HCAECs.
  
  
  METHODS
  We tested gene and protein expression changes in HCAECs in response to abacavir, didanosine and tenofovir using quantitative real-time reverse transciptase PCR, FACS and ELISA. The assessed genes/proteins included the proinflammatory molecules VCAM-1, ICAM-1, MCP-1, RANTES and IL-6. In addition, we assessed the gene expression of the intracellular reactive oxygen producing NADPH oxidase subunit gp91(PHOX) and the apoptosis regulating molecules Bcl-2 and BAD.
  
  
  RESULTS
  Exposure of HCAECs to abacavir, didanosine and tenofovir resulted in no statistically significant changes in any of the tested genes/proteins at any time point or at any concentration.
  
  
  CONCLUSIONS
  We found no evidence that abacavir, didanosine or tenofovir had direct in vitro effects on coronary endothelial cell gene transcription and protein expression of the selected mediators. If abacavir or didanosine increase cardiovascular risk, it is likely not through the direct endothelial activation pathways tested in these experiments. However, further studies are needed to completely exclude the toxicity of abacavir or didanosine on endothelial cells.
authors.affiliation: Department of Cellular & Integrative Physiology, Indiana Center for Vascular Biology & Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Chul
authors.initials: C
authors.lastname: Kim
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Linden
authors.initials: L
authors.lastname: Green
authors.forename: Brian M
authors.initials: BM
authors.lastname: Taylor
authors.forename: Maja
authors.initials: M
authors.lastname: Deuter-Reinhard
authors.forename: Zeruesenay
authors.initials: Z
authors.lastname: Desta
authors.forename: Matthias
authors.initials: M
authors.lastname: Clauss
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000209:etiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D016049:Didanosine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D061251:Primary Cell Culture; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000068698:Tenofovir; D000099227:Abacavir
chemical_list: D000225:Adenine; D019380:Anti-HIV Agents; D015815:Cell Adhesion Molecules; D016207:Cytokines; D016049:Didanosine; D015224:Dideoxynucleosides; D019255:NADPH Oxidases; D063065:Organophosphonates; D011518:Proto-Oncogene Proteins; D000068698:Tenofovir; D000099227:Abacavir