Adiponectin mediates the suppressive effect of rosiglitazone on plasminogen activator inhibitor-1 production

被引:30
作者
Hoo, Ruby L. C.
Chow, W. S.
Yau, M. H.
Xu, A.
Tso, Annette W. K.
Tse, H. F.
Fong, Carol H. Y.
Tam, Sidney
Chan, Lawrence
Lam, Karen S. L.
机构
[1] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Peoples R China
[2] Univ Hong Kong, Fac Med, LKS, Res Ctr Heart Brain Hormone & Hlth Aging, Hong Kong, Peoples R China
[3] Queen Mary Hosp, Clin Biochem Unit, Hong Kong, Peoples R China
[4] Baylor Coll Med, Div Endocrinol Diabet & Metab, Dept Med, Houston, TX 77030 USA
[5] Baylor Coll Med, Div Endocrinol Diabet & Metab, Dept Mol & Cellular Biol, Houston, TX 77030 USA
关键词
obesity; hyperglycemia; adipokines; thrombotic dieases;
D O I
10.1161/ATVBAHA.107.152462
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective - The purpose of this study was to examine the effects of PPAR-gamma agonist rosiglitazone, relative to sulfonylureas, on circulating levels of adiponectin and the prothrombotic factor, plasminogen activator inhibitor (PAI)-1, in type 2 diabetic patients, and to investigate, in animal models, whether the antithrombotic action of rosiglitazone was mediated through adiponectin. Methods and Results - Our clinical study (n=64) showed that after 24-week add-on therapy, the rosiglitazone group had a greater mean reduction in plasma PAI-1 levels (25%, versus 12% in sulfonylurea group, P=0.002). Stepwise multiple linear regression analysis identified the reduction in plasma fasting glucose and the rise in adiponectin levels to be independently associated with the reduction in PAI-I concentration in the rosiglitazone-treated patients. Rosiglitazone (20 mg/kg/d) reduced adipose tissue PAI-1 mRNA expression and its plasma levels in wild-type C57 mice with diet-induced obesity (P < 0.001), but this suppressive effect was attenuated in adiponectin knockout mice. Adenovirus-mediated overexpression of adiponectin led to a significant suppression of adipose tissue PAI-1 expression and its circulating concentrations in db/db diabetic mice. Our in vitro study demonstrated that recombinant adiponectin directly inhibited PAI-1 production in 3T3-L1 adipocytes. Conclusions - The antithrombotic effect of rosiglitazone is mediated, at least in part, through the suppressive effect of adiponectin on PAI-1 production.
引用
收藏
页码:2777 / 2782
页数:6
相关论文
共 37 条
[1]  
ASO Y, IN PRESS DIABET MED
[2]   Stromal cells are the main plasminogen activator inhibitor-1-producing cells in human fat - Evidence of differences between visceral and subcutaneous deposits [J].
Bastelica, D ;
Morange, P ;
Berthet, B ;
Borghi, H ;
Lacroix, O ;
Grino, M ;
Juhan-Vague, I ;
Alessi, MC .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (01) :173-178
[3]   Role of cytokines in the regulation of plasminogen activator inhibitor-1 expression and secretion in newly differentiated subcutaneous human adipocytes [J].
Birgel, M ;
Gottschling-Zeller, H ;
Röhrig, K ;
Hauner, H .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2000, 20 (06) :1682-1687
[4]   Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes [J].
Bodles, Angela M. ;
Banga, Anannya ;
Rasouli, Neda ;
Ono, Fumiyo ;
Kern, Philip A. ;
Owens, Randall J. .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2006, 291 (05) :E1100-E1105
[5]   Role of macrophage tissue infiltration in metabolic diseases [J].
Bouloumié, A ;
Curat, CA ;
Sengenès, C ;
Lolmède, K ;
Miranville, A ;
Busse, R .
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE, 2005, 8 (04) :347-354
[6]   Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes [J].
Chen, BY ;
Lam, KSL ;
Wang, Y ;
Wu, DH ;
Lam, MC ;
Shen, JG ;
Wong, LC ;
Hoo, RLC ;
Zhang, JL ;
Xu, AM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 341 (02) :549-556
[7]   Hypoadiponectinemia as a predictor for the development of hypertension - A 5-year prospective study [J].
Chow, Wing-Sun ;
Cheung, Bernard M. Y. ;
Tso, Annette W. K. ;
Xu, Aimin ;
Wat, Nelson M. S. ;
Fong, Carol H. Y. ;
Ong, Liza H. Y. ;
Tam, Sidney ;
Tan, Kathryn C. B. ;
Janus, Edward D. ;
Lam, Tai-Hing ;
Lam, Karen S. L. .
HYPERTENSION, 2007, 49 (06) :1455-1461
[8]   Obesity and thrombosis [J].
Darvall, K. A. L. ;
Sam, R. C. ;
Silverman, S. H. ;
Bradbury, A. W. ;
Adam, D. J. .
EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY, 2007, 33 (02) :223-233
[9]   A comparison of the effects of pioglitazone and rosiglitazone combined with glimepiride on prothrombotic state in type 2 diabetic patients with the metabolic syndrome [J].
Derosa, G ;
Cicero, AFG ;
Gaddi, A ;
Ragonesi, PD ;
Piccinni, MN ;
Fogari, E ;
Salvadeo, S ;
Ciccarelli, L ;
Fogari, R .
DIABETES RESEARCH AND CLINICAL PRACTICE, 2005, 69 (01) :5-13
[10]   Plasminogen activator inhibitor type I increases neointima formation in balloon-injured rat carotid arteries [J].
DeYoung, MB ;
Tom, C ;
Dichek, DA .
CIRCULATION, 2001, 104 (16) :1972-1977