Abstract
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, subconfluent HepG2 cells were incubated with triglyceride-rich particles (TGRP) isolated from Intralipid for 16 h, and PAI-1 levels were determined in conditioned medium using a specific ELISA. TGRP (1 to 6 mg triglycerides/ml) concentration-dependently increased PAI-1 secretion by cells, concomitantly with significant increases in intracellular triglyceride (TG) levels. Fatty acid analysis indicated that the incubation of cells with 3 mg of TG per ml of TGRP induced significant accumulation of 18:2 n-6 (linoleic acid, LA) and 18:3 n-3 (linolenic acid) reflecting the fatty acid composition at the added triglycerides. We then tested the comparative effects on PAI-1 secretion by HepG2 cells of LA and 18:1 n-9 (oleic acid, OA). LA, as a bovine serum albumin (BSA) complex, concentration-dependently (1 to 35 mumol/L) increased the secretion of PAI-1 by cells, whereas OA-BSA only minimally affected it at the highest concentration used (35 mumol/L). Incorporation of LA into cell pools, in the presence of increasing concentration of the FA in the medium, was studied by the use of a preparation containing [14C]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 concluded that PAI-1 secretion in HepG2 cells is modulated by triacylglycerols and by linoleic acid and/or its metabolic products.
Highlights
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
A nested case-control analysis of 60 atherosclerotic patients at higher risk of thrombosis who suffered from coronary cerebral and/or peripheral ischemic events during the first year of follow-up showed impaired fibrinolytic activity, secondary to PAI1 elevation, in the PLAT study [10].several established risk factors for coronary heart disease are associated with altered fibrinolytic function and,with elevated serum levels of PAI-1 ( 11).A positive correlation between plasma levels of triglyceride-rich lipoproteins and PAI-1 has been described by several authors including our group [11,12,13,14]
The activity of the fibrinolytic system is controlled by two homologous proteins, namely aTantiplasmin, Abbreviations: PAI-1, plasminogen activator inhibitor type 1 ; 11-PA, urokinase-type plasminogen activator; very low density lipoproteins (VLDL), very low density lipoprotein; TG, triglyceride; PL, phospholipid; FA, fatty acid; AA, arachidonic acid; TL, total lipid; TGRP, triglyceride-rich particles; LA,linoleic acid; OA, oleic acid; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; UI, unsaturation index; BSA, bovine serum albumin; TIC, thin-layer chromatography; HPLC:, high pressure liquid chromatography
Summary
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. In this study we have evaluated the effects of apolipoprotein-free triglyceride-rich particles (TGRP) on the secretion of PAI-I by HepG2 cells.
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