title: Plasminogen activator inhibitor type 1 (PAI-1) in plasma and adipose tissue in HIV-associated lipodystrophy syndrome. Implications of adipokines.
abstract: BACKGROUND
  PAI-1, an important inhibitor of fibrinolysis, is increased in obese subjects and has been shown to be an independent risk factor for cardiovascular disease. In the present study, we investigated the association between circulating levels of PAI-1 and locally produced PAI-1 in adipose tissue and body fat distribution and adipokines (TNF-alpha, TNF receptors, IL-6, IL-8) in patients with and without HIV-associated lipodystrophy syndrome (HALS).
  
  
  METHODS
  Eighteen men with HALS and 18 men with HIV but without HALS were investigated. DEXA and computed tomography scan were performed to determine total body fat and visceral adipose tissue mass. Insulin sensitivity was determined by the euglycaemic clamp technique. Plasma levels of PAI-1 and cytokines were determined. In addition, PAI-1, TNF-alpha, IL-6 and IL-8 mRNA levels in subcutaneous adipose tissue were measured by real-time reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  HALS patients were characterized by a 3-fold increased visceral adipose tissue (P < 0.001) and reduced limb fat (P < 0.01) as compared with non-HALS patients but with no difference in total fat mass between the groups. Plasma PAI-1 was increased in HALS patients (16.7 ng mL(-1) vs. 8.2 ng mL(-1), P < 0.05). Plasma PAI-1 was positively correlated with BMI (r = 0.74, P < 0.01), plasma TNF-alpha level (r = 0.64, P < 0.01), sTNFR-I (r = 0.38, P < 0.05), and visceral fat (r = 0.67, P < 0.01). Moreover, plasma PAI-1 was negatively associated with insulin sensitivity (r = -0.57, P < 0.01) and the percentage of limb fat (r = -0.57, P < 0.01). A positive correlation was found between plasma PAI-1 and TNF-alpha mRNA level. No association was, however, found between plasma PAI-1 and PAI-1 mRNA level in adipose tissue.
  
  
  CONCLUSIONS
  Plasma PAI-1 is increased in HALS patients and it is suggested that dysregulation of the TNF-system (high TNFalpha and high sTNFR1) may play a role in up-regulating PAI-1 in HALS.
authors.affiliation: Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: G
authors.initials: G
authors.lastname: He
authors.forename: O
authors.initials: O
authors.lastname: Andersen
authors.forename: S B
authors.initials: SB
authors.lastname: Haugaard
authors.forename: A S
authors.initials: AS
authors.lastname: Lihn
authors.forename: S B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: S
authors.initials: S
authors.lastname: Madsbad
authors.forename: B
authors.initials: B
authors.lastname: Richelsen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D015992:Body Mass Index; D016207:Cytokines / Q000032:analysis* / Q000097:blood; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D016209:Interleukin-8 / Q000032:analysis / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000097:blood; D015842:Serine Proteinase Inhibitors / Q000032:analysis* / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D015842:Serine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha