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(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

Thomas Skurk; Yu-Mi Lee; Hans Hauner

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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