(Hypertension. 2001;37:1336.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Angiotensin II and Its Metabolites Stimulate PAI-1 Protein Release From Human Adipocytes in Primary Culture
From the Clinical Department, German Diabetes Research Institute, Düsseldorf, Germany.
Correspondence to Dr Hans Hauner, German Diabetes Research Institute, Clinical Department, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. E-mail hauner{at}dfi.uni-duesseldorf.de
Abstract—Plasminogen activator inhibitor (PAI)-1 is the main inhibitor of the fibrinolytic system and was recently shown to be produced by adipose cells. Obesity is associated with an increased production and release of PAI-1 protein. The aim of this study was to investigate the role of angiotensin (Ang) II and its degradation products for PAI-1 release from human adipose cells. For this purpose, we used the model of in vitro differentiated human adipocytes in primary culture. Exposure of human adipocytes to Ang II resulted in a dose- and time-dependent stimulation of PAI-1 release into the culture medium. The maximum effect of Ang II was found at a concentration of 10-5 mol/L for 48 hours, increasing PAI-1 release by 276±53% compared with control cultures (P<0.05). This stimulation was preceded by an increase in specific PAI-1 mRNA copies by 65±12% (P<0.05), with a maximum after 6 hours. Incubation of adipocytes with 10-5 mol/L Ang III and Ang IV, respectively, also resulted in a stimulation of PAI-1 release into the medium by 195±60% (P<0.05) and 142±24% (P<0.05), respectively, compared with control cultures. Addition of the angiotensin-receptor subtype 1 (AT1) blocker candesartan abolished the stimulatory action of Ang II and its metabolites, indicating that this effect is mediated by AT1. Addition of the AT1 blocker alone to unstimulated cultures reduced PAI-1 release by 41%±25% (P<0.05), suggesting that endogenous Ang II synthesis contributes to PAI-1 secretion from adipose tissue in an autocrine/paracrine manner. In conclusion, Ang II and its metabolites promote PAI-1 production and release by human fat cells and may contribute to the impairment of the fibrinolytic system typical for obesity. AT1 receptor blockade reduces basal and abolishes Ang II–stimulated PAI-1 release from human adipocytes.
Key Words: plasminogen • adipose • obesity • angiotensin • receptors, angiotensin
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