title: HIV vasculopathy: role of mononuclear cell-associated Krüppel-like factors 2 and 4.
abstract: OBJECTIVE
  To determine the relationships between Krüppel-like factors (KLF) 2 and 4, immune-activation, and subclinical vascular disease in HIV-infected patients on antiretroviral therapy (ART).
  
  
  METHODS
  Double-blind, randomized, placebo-controlled trial.
  
  
  METHODS
  We studied 74 HIV-infected adults on ART enrolled in a randomized clinical trial of statin therapy. KLF2 and KLF4 gene expression was measured by quantitative PCR from peripheral blood mononuclear cells (PBMCs) at baseline and after 24 weeks of 10 mg daily rosuvastatin or placebo. At the same time points, T-cell and monocyte activation were assessed by flow cytometry and vascular health was assessed by cardiac computed tomography and carotid ultrasound.
  
  
  RESULTS
  KLF4 expression was negatively correlated with duration of ART (r = -0.351, P = 0.004) and positively correlated with measures of immune activation: proinflammatory monocytes [CD14CD16 (r = 0.343, P = 0.003)], patrolling monocytes [CD14CD16 (r = 0.276, P = 0.017)], and activated CD8 T-lymphocytes [CD8DRCD38 (r = 0.264, P = 0.023)]. KLF2 expression was negatively correlated with subclinical atherosclerosis: mean-mean common carotid artery intima-media thickness (r = -0.231, P = 0.048), mean-max carotid artery intima-media thickness (r = -0.271, P = 0.020), and coronary artery calcium score (r = -0.254, P = 0.029). There were no statistically significant changes in KLF2/4 expression in PBMCs after 24 weeks of rosuvastatin.
  
  
  CONCLUSIONS
  Expression of KLF4 in PBMCs positively correlates with cellular markers of immune activation, whereas KLF2 expression negatively correlates with markers of subclinical atherosclerosis in this HIV-infected population on ART. Additional studies are needed to determine if targeted interventions might alter KLF2/4 expression to reduce inflammation and vascular risk in humans.
authors.affiliation: aCase Western Reserve University School of Medicine bUniversity Hospitals Harrington Heart and Vascular Institute cDepartment of Biostatistics, Case Western Reserve University dDivision of Infectious Diseases, Rainbow Babies and Children's Hospital eLouis Stokes Veteran's Administration Medical Center, Cleveland, Ohio, USA. *Drs Andrew T. Hale and Chris T. Longenecker contributed equally to the writing of this article.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hale
authors.forename: Chris T
authors.initials: CT
authors.lastname: Longenecker
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Sara M
authors.initials: SM
authors.lastname: Debanne
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Labatto
authors.forename: Norma
authors.initials: N
authors.lastname: Storer
authors.forename: Anne
authors.initials: A
authors.lastname: Hamik
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D004311:Double-Blind Method; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000150:complications*; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D006949:Hyperlipidemias / Q000517:prevention & control*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D060888:Real-Time Polymerase Chain Reaction; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography
chemical_list: D044966:Anti-Retroviral Agents; D000924:Anticholesteremic Agents; C096161:KLF2 protein, human; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D010919:Placebos; D000068718:Rosuvastatin Calcium