Published online before print February 20, 2003, doi: 10.1161/01.ATV.0000062885.61917.A5
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© 2003 American Heart Association, Inc.
Thrombosis |
Regulation of Plasma PAI-1 Concentrations in HAART-Associated Lipodystrophy During Rosiglitazone Therapy
From the Department of Medicine, Divisions of Diabetes (H.Y.-J., J.S.) and Infectious Diseases (J.S.), Helsinki University Central Hospital, Helsinki, Finland; the Department of Medicine, Atherosclerosis Research Unit (H.Y.-J., A.S., R.M.F., K.K., E.E., P.E., A.H.), King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden; and the Minerva Research Institute (E.K.), Helsinki, Finland.
Correspondence to Jussi Sutinen, MD, Department of Medicine, Helsinki University Central Hospital, PO Box 348, FIN-00029 HUS, Helsinki, Finland. E-mail jussi.sutinen{at}hus.fi
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.
Methods and 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.
Key Words: fibrinolysis • tissue plasminogen activator • steatosis • insulin • triglycerides
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