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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:173.)
© 2002 American Heart Association, Inc.

Thrombosis

Stromal Cells Are the Main Plasminogen Activator Inhibitor-1-Producing Cells in Human Fat

Evidence of Differences Between Visceral and Subcutaneous Deposits

Delphine Bastelica; Pierre Morange; Bruno Berthet; Hélène Borghi; Odile Lacroix; Michel Grino; Irène Juhan-Vague; Marie-Christine Alessi

From the Laboratoire d’Hématologie (D.B., P.M., I.J.-V., M.-C.A.), EPI 99-36, and Service Commun de Microscopie Electronique (H.B.), Faculté de Médecine Timone; Service de Chirurgie Digestive (B.B.), Centre Hospitalier Universitaire Timone; and INSERM U501 (O.L., M.G.), Faculté de Médecine Nord, Marseille, France.

Reprint requests to Prof M.C. Alessi, Laboratory Hematology, EPI 9936, Faculty of Medicine, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France. E-mail Marie-Christine.Alessi{at}medecine.univ-mrs.fr

Elevated plasma plasminogen activator inhibitor (PAI)-1 observed during insulin resistance has been connected with an excessive PAI-1 adipose tissue secretion mainly by visceral fat. Our aim was to compare the localization of PAI-1 in human visceral and subcutaneous fats. PAI-1 secretion was also investigated in vitro during human adipocyte differentiation. PAI-1 antigen and mRNA were localized in the stromal area of the tissue and were also present in a few CD14-positive monocytes, in direct contact with adipocytes. In addition, in subcutaneous tissue, PAI-1 mRNA contents, determined by using real-time polymerase chain reaction, were higher in the stromal fraction than in the adipocyte fraction. PAI-1 mRNA-positive cells were 5-fold more frequent in the visceral area than in the subcutaneous stromal area (P=0.004). Such a difference was also observed for PAI-1 mRNA content between both whole adipose tissues. In contrast to leptin, during adipocyte differentiation, PAI-1 secretion did not follow adipocyte maturation. In situ hybridization in culture did not reveal PAI-1 mRNA in lipid-filled cells. Our results demonstrate that PAI-1 production is mainly due to stromal cells, which were more numerous in the visceral than in the subcutaneous depot. These results could explain the strong relationship observed between circulating PAI-1 levels and the accumulation of visceral fat.

Key Words: fibrinolysis • obesity • differentiation • visceral fat • real-time polymerase chain reaction Taqman