Regulation of Plasma PAI-1 Concentrations in HAART-Associated Lipodystrophy During Rosiglitazone Therapy.
Yki-Jarvinen, Hannele; Sutinen, Jussi; Silveira, Angela; Korsheninnikova, Elena; Fisher, Rachel M.; Kannisto, Katja; Ehrenborg, Ewa; Eriksson, Per; Hamsten, Anders
Arteriosclerosis, Thrombosis & Vascular Biology.
23(4):688-694, April 2003.
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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.
(C) 2003 American Heart Association, Inc.