Effect of a-tocopherol on LDL oxidation and glycation : in vitro and in vivo studies

Much data support a role for both low density lipoprotein (LDL) oxidation and glycation in atherogenesis. While a-tocopherol decreases the oxidative susceptibility of LDL, its role in decreasing LDL glycation is unclear. Hence we tested the effect of a-tocopherol both in vitro and in vivo on LDL oxidation and glycation. LDL was isolated after enrichment of plasma with a-tocopherol. This resulted in a 2-fold increase in a-tocopherol in LDL (AT-LDL). During a 6day incubation of control LDL (C-LDL) and AT-LDL with 25 mM glucose, there were no significant differences in the degree of glycation on days 1, 3, and 6. Also, apoB advanced glycosylation end product levels were not significantly different between C-LDL and AT-LDL. There was a progressive increase in the susceptibility of LDL to oxidation with increasing LDL glycation as evidenced by reduced lag time of copper-catalyzed LDL oxidation. However, AT-LDL was more resistant to coppercatalyzed oxidation. Similar findings were observed when the LDLs were incubated with endothelial cells. I The data from the a-tocopherol supplementation study confirmed our in vitro findings that a-tocopherol significantly decreases oxidative susceptibility of LDL, but does not affect its glycation. Therefore, while glycation increases LDL oxidative susceptibility, a-tocopherol decreases the oxidation of glycated LDL but not LDL g1ycation. -Li, D. , S. Devaraj, C. Fuller, R Bucala, and I. Jialal. Effect of a-tocopherol on LDL oxidation and glycation: in vitro and in vivo studies. J. Lipid Res. 1996. 37: 1978-1986. Supplementary key words advanced glycosylation end products Plausible modifications of lipoproteins, such as LDL, include non-enzymatic glycation and oxidation (1). Several lines of evidence support a role for glycated LDL and advanced glycosylation end products (AGE) in the genesis of the atherosclerotic lesion (2,3). Furthermore, numerous laboratories have now documented that oxidatively modified LDL is pro-atherogenic and exists in vivo (4-6). a-Tocopherol, a potent, lipid soluble antioxidant, has been shown to decrease the susceptibility of LDL to oxidation both in vitro and after in vivo supplementation (7, 8). Furthermore, some studies have indicated that a-tocopherol might decrease protein glycation. Ceriello et al. (9, 10) have shown that in addition to a-tocopherol decreasing the glycation of albumin in vitro, supplementation with a-tocopherol decreased protein glycation in insulin-dependent diabetics (IDDM) in a dosedependent fashion. Furthermore, Aoki et al. (1 1 ) showed in diabetic rats that vitamin E supplementation decreased AGE formation as evidenced by a decrease in the thermal rupture time of collagen. However, Paolisso et al. (12, 13) have shown that while a-tocopherol supplementation in non-insulindependent diabetics (NIDDM) decreased protein glycation, this effect is possibly mediated by an improvement in insulin action resulting in a decrease in plasma glucose levels. In addition, two recent in vivo supplementation studies with a-tocopherol showed decreased LDL oxidative susceptibility, but no effect on protein glycation (14, 15). However, in both these studies the number of subjects was small and other factors in the in vivo environment could have obscured the effect of a-tocopherol on protein glycation. Furthermore, these studies examined the oxidative susceptibility of LDL without separating the glycated and non-glycated fractions. Thus, while a-tocopherol appears to have a clear role in decreasing the oxidative susceptibility of LDL, the evidence regarding its effect on protein glycation is unclear. The present study was undertaken to gain a better appreciation of the role of a-tocopherol on LDL oxidation and glycation. Accordingly, we tested the effect of a-tocopherol on LDL oxidative susceptibility and glycation, including AGE Abbreviations: LDL, low density lipoprotein; AGE, advanced glycosylation end products; IDDM, insulindependent diabetes mellitus; NIDDM, non-insulindependent diabetes mellitus; AT-LDL, a-tocopherol-enriched LDL; C-LDL, control LDL. 'Current address: Department of Food, Nutrition, and Food Service Management, The University of North Carolina at Greensboro, Greensboro, NC 27412. 'Current address: The Picower Institute for Medical Research, Manhasset, NY 11030. 'To whom correspondence should be addressed. 1978 Journal of Lipid Research Volume 37, 1996 by gest, on N ovem er 6, 2017 w w w . j.org D ow nladed fom modification, after enrichment of plasma with a-tocopherol in vitro, and also after in vivo supplementation in diabetic subjects. MATERIALS AND METHODS