The aim of the present study was to investigate the combined impact of visceral adipose tissue (VAT) and secretory group IIA phospholipase A(2) (sPLA(2)-IIA) concentrations on the atherogenicity of low-density lipoprotein (LDL) particles among men. Analyses were conducted in 74 mid-obese healthy men (age: (mean+/-s.d.) 37.9+/-11.7 years). Plasma levels of sPLA(2)-IIA were measured with a commercial ELISA and VAT levels were assessed by computed tomography. Distinct subpopulations of LDL particles were characterized from whole plasma using nondenaturating 2-16% gradient gel electrophoresis. Data indicated that plasma sPLA(2)-IIA levels were approximately 29% (P=0.007) higher among men characterized by a higher accumulation of VAT (>142 vs < or =142 cm(2)). Men having high plasma sPLA(2)-IIA levels (> or =127.2 ng/dl, the median value), were characterized by higher levels of plasma cholesterol (C) and apolipoprotein (apo) B, LDL-C, LDL-apoB, oxidized LDL (OxLDL) and by smaller LDL particles compared to men with sPLA(2)-IIA<127.2 ng/dl. Multiple regression analyses showed that plasma triglycerides and sPLA(2)-IIA levels explained 22.7 and 11.8% of the variance in LDL peak particle size, respectively. Levels of VAT and of sPLA(2)-IIA were the strongest correlates of OxLDL levels explaining, respectively, 15.0 and 5.5% of their variability. Both VAT and sPLA(2)-IIA levels modulate the atherogenecity of LDL by accounting for the reduction in their size and their susceptibility to oxidation.