Zirlik Andreas, Leugers Anne, Lohrmann Jens, Ernst Sandra, Sobel Burton E, Bode Christoph, Nordt Thomas K
Brigham and Women's Hospital, Harvard Medical School, Cardiovascular Medicine, Department of Medicine, Boston, Massachusetts 02115, USA.
Thromb Haemost. 2004 Apr;91(4):674-82. doi: 10.1160/TH03-06-0384.
Adipose tissue produces substantial amounts of plasminogen activator inhibitor type-1 (PAI-1), an established cardiovascular risk factor. This study evaluated PAI-1 expression in human adipose tissue in response to thiazolidinediones, insulin sensitising drugs activating peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Troglitazone, rosiglitazone, and ciglitazone significantly reduced PAI-1 protein expression in human preadipocytes under basal conditions and after stimulation of the cells with TGF-beta. Pioglitazone had no effect. In human adipocytes all four thiazolidinediones significantly attenuated PAI-1 expression. Signalling appeared to be mediated via PPAR-gamma and effects reflected, at least in part, changes in transcription. Accordingly, patients with insulin resistance may benefit from treatment with thiazolidinediones with respect to diminution of PAI-1 expression in adipose tissue and consequent potential reduction of cardiovascular risk.
脂肪组织会产生大量的纤溶酶原激活物抑制剂-1（PAI-1），这是一种已确定的心血管危险因素。本研究评估了噻唑烷二酮类药物（一类激活过氧化物酶体增殖物激活受体γ（PPAR-γ）的胰岛素增敏药物）对人脂肪组织中PAI-1表达的影响。在基础条件下以及用转化生长因子-β刺激细胞后，曲格列酮、罗格列酮和环格列酮显著降低了人前脂肪细胞中PAI-1蛋白的表达。吡格列酮没有效果。在人脂肪细胞中，所有四种噻唑烷二酮类药物均显著减弱了PAI-1的表达。信号传导似乎是通过PPAR-γ介导的，其作用至少部分反映了转录的变化。因此，胰岛素抵抗患者可能会从噻唑烷二酮类药物治疗中受益，这有助于减少脂肪组织中PAI-1的表达，并进而潜在降低心血管风险。
