title: Regulation of plasma PAI-1 concentrations in HAART-associated lipodystrophy during rosiglitazone therapy.
abstract: OBJECTIVE
  Patients with highly active antiretroviral therapy-associated lipodystrophy (HAART+LD+) have high plasminogen activator inhibitor-1 (PAI-1) concentrations for unknown reasons. We determined whether (1). plasma PAI-1 antigen concentrations are related to liver fat content (LFAT) independently of the size of other fat depots and (2) rosiglitazone decreases PAI-1 and LFAT in these patients.
  
  
  RESULTS
  In the cross-sectional study, 3 groups were investigated: 30 HIV-positive patients with HAART+LD+, 13 HIV-positive patients without lipodystrophy (HAART+LD-), and 15 HIV-negative subjects (HIV-). In the treatment study, the HAART+LD+ group received either rosiglitazone (8 mg, n=15) or placebo (n=15) for 24 weeks. Plasma PAI-1 was increased in HAART+LD+ (28+/-2 ng/mL) compared with the HAART+LD- (18+/-3, P<0.02) and HIV- (10+/-3, P<0.001) groups. LFAT was higher in HAART+LD+ (7.6+/-1.7%) than in the HAART+LD- (2.1+/-1.1%, P<0.001) and HIV- (3.6+/-1.2%, P<0.05) groups. Within the HAART+LD+ group, plasma PAI-1 was correlated with LFAT (r=0.49, P<0.01) but not with subcutaneous or intra-abdominal fat or serum insulin or triglycerides. In subcutaneous adipose tissue, PAI-1 mRNA was 2- to 3-fold higher in the HAART+LD+ group than in either the HAART+LD- or HIV- group. Rosiglitazone decreased LFAT, serum insulin, and plasma PAI-1 and increased serum triglycerides but had no effect on intra-abdominal or subcutaneous fat mass or PAI-1 mRNA.
  
  
  CONCLUSIONS
  Plasma PAI-1 concentrations are increased in direct proportion to LFAT in HAART+LD+ patients. Rosiglitazone decreases LFAT, serum insulin, and plasma PAI-1 without changing the size of other fat depots or PAI-1 mRNA in subcutaneous fat. These data suggest that liver fat contributes to plasma PAI-1 concentrations in these patients.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, PO Box 348, FIN-00029 HUS, Helsinki, Finland.
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
authors.forename: Jussi
authors.initials: J
authors.lastname: Sutinen
authors.forename: Angela
authors.initials: A
authors.lastname: Silveira
authors.forename: Elena
authors.initials: E
authors.lastname: Korsheninnikova
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Fisher
authors.forename: Katja
authors.initials: K
authors.lastname: Kannisto
authors.forename: Ewa
authors.initials: E
authors.lastname: Ehrenborg
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy; D006801:Humans; D006946:Hyperinsulinism / Q000139:chemically induced / Q000188:drug therapy; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000188:drug therapy; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D020738:Leptin / Q000096:biosynthesis / Q000235:genetics; D008060:Lipodystrophy / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D000077154:Rosiglitazone; D040521:Subcutaneous Tissue / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014157:Transcription Factors / Q000819:agonists
chemical_list: D015850:Interleukin-6; D020738:Leptin; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone