High levels of small, dense
LDL in plasma are associated with increased risk for
cardiovascular disease. There are some biochemical characteristics that may render small, dense
LDL particles more atherogenic than larger, buoyant
LDL particles. First, small, dense
LDL particles contain less
phospholipids and unesterified
cholesterol in their surface monolayer than do large, buoyant
LDL particles. This difference in
lipid content appears to induce changes in the conformation of
apolipoprotein B-100, leading to more exposure of
proteoglycan-binding regions. This may be one reason for the high-affinity binding of small, dense
LDL to arterial
proteoglycans. Reduction of the
phospholipid content in the surface monolayer
LDL by treatment with
secretory phospholipase A2 (
sPLA2) forms small, dense
LDL with an enhanced tendency to interact with
proteoglycans. Circulating levels of sPLA2-IIA appears to be an independent risk factor for
coronary artery disease and a predictor of cardiovascular events. In addition, in-vivo studies support the hypothesis that
sPLA2 proteins contribute to
atherogenesis and its clinical consequences. These data suggest that modification of
LDL by
sPLA2 in the arterial tissue or in plasma may be a mechanism for the generation of atherogenic
lipoprotein particles in vivo, with a high tendency to be entrapped in the arterial extracellular matrix.