title: SIV/SHIV Infection Triggers Vascular Inflammation, Diminished Expression of Krüppel-like Factor 2 and Endothelial Dysfunction.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) infection is associated with increased risk of thromboembolic and cardiovascular comorbid conditions. Although systemic inflammation is linked to cardiovascular risk, direct evidence of vascular inflammation and endothelial dysfunction is lacking.
  
  
  METHODS
  We examined by immunofluorescence microscopy thoracic aortas from 16 simian immunodeficiency virus (SIV)- or simian-human immunodeficiency virus (SHIV)-infected and 16 uninfected rhesus macaques.
  
  
  RESULTS
  Focal endothelial proliferation and subendothelial inflammatory cells were found in sections of all infected animals, compared with minimal changes in sections from the 16 uninfected controls. In the infected animals, we detected increased endothelial levels of bacterial 16s ribosomal DNA as well as increased subendothelial accumulation of CD68(+) monocytes/macrophages (P< .001) and CD8(+) T lymphocytes (P< .001). Endothelial dysfunction was manifested by decreased levels of endothelial nitric oxide synthase (P< .005) and Krüppel-like factor 2 (KLF2) (P< .005). KLF2 expression was decreased in primary human aortic endothelial cells exposed to bacterial lipopolysaccharide or to oxidized low-density lipoprotein in vitro, and this could be prevented by simvastatin.
  
  
  CONCLUSIONS
  SIV and SHIV infection lead to endothelial inflammation, dysfunction, and decreased KLF2 expression reflecting early atherosclerotic changes. Translocated bacterial components and lipid oxidation products may induce endothelial dysfunction in HIV infection that could be prevented by statin treatment.
authors.affiliation: Case Western Reserve University/University Hospitals/Case Medical Center.
authors.forename: Soumya
authors.initials: S
authors.lastname: Panigrahi
authors.affiliation: Case Western Reserve University/University Hospitals/Case Medical Center.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Freeman
authors.affiliation: School of Health and Rehabilitation Sciences, Ohio State University, Columbus.
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Funderburg
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Mudd
authors.affiliation: Case Western Reserve University/University Hospitals/Case Medical Center.
authors.forename: Souheil A
authors.initials: SA
authors.lastname: Younes
authors.affiliation: Case Western Reserve University/University Hospitals/Case Medical Center.
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
authors.affiliation: Case Western Reserve University/University Hospitals/Case Medical Center.
authors.forename: David A
authors.initials: DA
authors.lastname: Zidar
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, Georgia.
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, Georgia.
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.affiliation: Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Calabrese
authors.affiliation: Neuroinflammation Research Center, Cleveland Clinic.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Ransohoff
authors.affiliation: Case Western Reserve University/University Hospitals/Case Medical Center.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
authors.affiliation: Case Western Reserve University/University Hospitals/Case Medical Center.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000032:analysis; D004730:Endothelium, Vascular / Q000276:immunology* / Q000382:microbiology; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000276:immunology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology*
chemical_list: D004269:DNA, Bacterial; D051741:Kruppel-Like Transcription Factors
keywords: KLF2; LPS; SHIV; SIV; eNOS; endothelial dysfunction; immunohistochemistry; oxLDL; simvastatin