LINOLEIC-ACID ENHANCES THE SECRETION OF PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 BY HEPG2 CELLS

This study was undertaken in order to assess whether triglycerides and /or their fatty acids directly influence the secretion of plasminogen activator inhibitor type 1 (PAI-1) in HepG2 cells. To this end, subcon fluent HepG2 cells were incubated with triglyceride-rich particles (TG RP) isolated from Intralipid(R) for 16 h, and PAI-1 levels were determ ined in conditioned medium using a specific ELISA. TGRP (1 to 6 mg tri glycerides/ml) concentration-dependently increased PAI-1 secretion by cells, concomitantly with significant increases in intracellular trigl yceride (TG) levels. Fatty acid analysis indicated that the incubation of cells with 3 mg of TG per ml of TGRP induced significant accumulat ion of 18:2 n-6 (linoleic acid, LA) and 18:3 n-3 (linolenic acid), ref lecting the fatty acid composition of the added triglycerides. We then tested the comparative effects on PAI-1 secretion by HepG2 cells of L A and 18:1 n-9 (oleic acid, OA). LA, as a bovine serum albumin (BSA) c omplex, concentration-dependently (1 to 35 mu mol/L) increased the sec retion of PAI-1 by cells, whereas OA-BSA only minimally affected it at the highest concentration used (35 mu mol/L). Incorporation of LA int o cell pools, in the presence of increasing concentration of the FA in the medium, was studied by the use of a preparation containing [C-14] LA. LA accumulated in all lipid classes including diacylglycerol, the incorporated LA being converted into arachidonic acid (AA) as assessed by HPLC radiochromatography of the fatty acid methyl esters. It is co ncluded that PAI-1 secretion in HepG2 cells is modulated by triacylgly cerols and by linoleic acid and/or its metabolic products.