Low-density lipoprotein particle size is inversely related to plasminogen activator inhibitor-1 levels - The Insulin Resistance Atherosclerosis Study

High levels of plasminogen activator inhibitor-1 (PAI-1) and preponderance of small dense low-density lipoproteins (LDL) have both been associated wit h atherosclerotic disease and with the insulin resistance syndrome (IRS). I n vitro studies have shown a stimulatory effect of various lipoproteins on PAI-1 release from different cells, including endothelial cells and adipocy tes. The authors sought to investigate the relation of PAI-1 to LDL particl e size in a large tri-ethnic population (n = 1549) across different states of glucose tolerance. LDL size was determined by gradient gel electrophores is, 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=-0.2 1, P<0.0001), independent of gender and ethnicity. However, the authors fou nd a significant interaction with glucose tolerance status (P=0.035). In un ivariate analysis, the association between PAI-I and LDL size was most pron ounced in subjects with normal glucose tolerance (NGT, r=-0.22, P<0.0001) a nd weaker in impaired glucose tolerance (IGT, r=-0.12, P=0.03) and type-2 d iabetes (r=-0,10, P=0.02). After adjustment for demographic variables and m etabolic variables known to influence PAI-I levels (triglyceride and insuli n 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 s ize seem to contribute more importantly to PAI-1 levels. The demonstrated i nverse relation of LDL size and PAI-1 levels provides one possible explanat ion for the atherogeneity of small dense LDL particles.