Greater oxidative susceptibility of the surface monolayer in small dense LDL may contribute to differences in copper-induced oxidation among LDL density subfractions.

We monitored peroxidative stress in the surface gested to contribute to the increased atherosclerosis risk monolayer as compared with the outer core of large, buoyant (d 1.025-1.032 g/ml) and small, dense (d 1.040-1.054 g/ml) low den- sity lipoprotein (LDL) subfractions using the oxidation-labile fluorescent probes parinaric acid (PnA) and parinaric acid methyl ester (PnME), which partition preferentially into these respective regions of LDL. Oxidation was initiated either with CuSOr (5 pM) or the iron (Fe3+)-containing lipophilic complex hemin (1.0 pM) plus cumene hydroperoxide to facilitate heme degradation. In the presence of Cu2+, PnA was depleted significantly more rapidly than PnME in dense (P = 0.039) but not in buoyant LDL, suggesting that surface vulnerability is en- hanced in dense LDL particles. With hemin, PnA and PnME were similarly susceptible within both subfractions, although there was a trend toward slower loss of PnA in buoyant LDL (P = 0.10), consistent with the internal site of initiation and a greater surface resistance in buoyant particles. As indicated by conjugated diene lag times, dense LDL was more susceptible than buoyant LDL to oxidation by Cu2+ (P = 0.03) but not he- min (P = 0.68). m These results suggest that the increased susceptibility of dense LDL to oxidation by external agents such as Cu2' is at least partially mediated by an enhanced vulnerabil- ity of the surface compartment.-Tribble, D. L., R M. Krauss, M. G. Lansberg, P. M. Thiel, and J. J. M. van den Berg. Greater oxidative susceptibility of the surface monolayer in small dense LDL may contribute to differences in copper- induced oxidation among LDL density subfractions. J. Lipid Res. 1995. 36: 662-671. Supplementary key worrLE LDL small dense LDL hemin parinaric acid oxidation fluomscent probes large buoyant