INTRODUCTION

         The Process of atherosclerosis begins with the transport of lipoproteins, specially LDL, into artery wall. The quantity of LDL transpped in the artery wall is directly proportional to the concentration of circulating lipoproteins. The trapped LDL are modified by a superoxide-dependent process, and lipid oxidation is initiated within the LDL particle. Convincing evidence suggests that oxidative modification of LDL plays an important role in the pathophysiology of atherogenesis. In recent years, numerous molecular mechanisms have been proposed to explain the different oxidation pathways that lead to modification of LDL. One of the earliest steps in the generation of oxidatively modified LDL is the peroxidation of its polyunsaturated fatty acids (PUFA). The oxidative breakdown products of these fatty acids, such as malondialdehydeand 4 - hydroxynonenal, form covalent bands with apolipoprotien B (apo B) by specifically modifiying lysine residues. Macrophages internalize modified LDL at a faster rate than they internalize native LDL via a specific scavenger receptor - mediated pathway. In vitro studies have shown that acetyl - LDL receptors do not recognize unmodified LDL, nor is uptake via these receptors down regulated by internal macrophage cholesterol content. Accumulation of lipids can lead to a conversation of macrophages into lipid-laden foam cells, typical constituents of fatty streaks and atherosclerotic plaques. Thus in addition to lowering the levels of circulating LDL, decreasing the susceptibility of LDL to oxidative modification ,may also impede development of atherosclerosis. One effective strategy of reducing atherosclerosis and coronary heart disease (CHD) risk is to alter plasma lipid and lipoprotein profiles by manipulating the type and amount of dietary fat. Recent studies have reported that diets rich in monounsaturated fatty acids (MUFA) result in LDL that are less readily oxidized than LDL isolated from subjects who consume diets rich in PUFA. Dietary saturated fatty acids (SFA) adversely affect plasma lipids, lipoproteins, hemostatic factors as well as susceptibility of LDL to oxidation. However, a recent study reported that replacing SFA with either MUFA or PUFA in diets that provide less total fat (i.e.,-30%energy) did not appreciably affect LDL oxidative susceptibility as measured only by lag time. We are unaware of any studies that have examined the effects of decreasing dietary total fat and SFA, whereas holding MUFA and PUFA levels constant, an LDL oxidative status. This is of relevance because current dietary guidelines for cardiovascular disease recommend decreasing both dietary SFA and total fat. Thus, the present study was conducted to evaluate whether a step-wise reduction in total fat and SFA could change the lipid composition of LDL, and as a result, change LDL oxidative susceptibility withoutthe poptential confounding effects of different levels of MUFA and PUFA.

 

 

Hosted by www.Geocities.ws

1