Low-Density Lipoprotein Particle Size Is Inversely Related to Plasminogen Activator Inhibitor-1 Levels

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Abstract
Abstract —High levels of plasminogen activator inhibitor-1 (PAI-1) and preponderance of small dense low-density lipoproteins (LDL) have both been associated with atherosclerotic disease and with the insulin resistance syndrome (IRS). In vitro studies have shown a stimulatory effect of various lipoproteins on PAI-1 release from different cells, including endothelial cells and adipocytes. The authors sought to investigate the relation of PAI-1 to LDL particle size in a large tri-ethnic population (n=1549) across different states of glucose tolerance. LDL size was determined by gradient gel electrophoresis, and PAI-1 was measured by a 2-site immunoassay, sensitive to free PAI-1. PAI-1 was inversely related to LDL size in the overall population (r=−0.21, P P =0.035). In univariate analysis, the association between PAI-1 and LDL size was most pronounced in subjects with normal glucose tolerance (NGT, r=−0.22, P P =0.03) and type-2 diabetes (r=−0.10, P =0.02). After adjustment for demographic variables and metabolic variables known to influence PAI-1 levels (triglyceride and insulin sensitivity), a significant inverse relation of LDL size to PAI-1 levels was only present in NGT ( P =0.023). In subjects with IGT or overt diabetes, who usually have elevated PAI-1 levels, additional factors other than LDL size seem to contribute more importantly to PAI-1 levels. The demonstrated inverse relation of LDL size and PAI-1 levels provides one possible explanation for the atherogeneity of small dense LDL particles.