Lipoproteins and Atherogenesis

Abstract

The frontiers in atherosclerosis research are moving from lipoprotein metabolism and control of hyperlipidemia to the cellular events in the artery wall. Emerging hypotheses, including the oxidative modification hypothesis, are already suggesting new approaches that could complement and be additive to control of hypercholesterolemia in the prevention of atherosclerosis.

The Role of Oxidized LDL in the Atherogenic Process

“…Atherosclerosis is a complex and multifactorial disease that is the result of interactions between many genetic and environmental influences (1,2). The rupture of an atherogenic plaque resulting in thrombus formation that occludes a coronary vessel is only the final step in a complex series of events that ultimately leads to clinical events.…”

“…The fatty streak, through a series of as yet undefined steps, then progresses into the more complex atherosclerotic plaque, which is covered by a fibrous cap which isolates the potentially toxic debris of dead and dying cells. However, in some cases the fibrous cap is breached, and plaque rupture and thrombosis occurs, leading to clinical events such as myocardial infarction (1)(2)(3).…”

“…It was an effort to understand the initial accumulation of cholesterol within the foam cell that led to the concept that modification of LDL was a necessary step for foam cell formation (1,(4)(5). Data indicated that in the early fatty streak the vast majority of foam cells were of macrophage origin.…”

“…It is now clear that all of the cells of the artery wall, including endothelial cells, smooth muscle cells and macrophage themselves, have the capacity to oxidatively modify LDL (1,5). In turn, there appear to be a family of "scavenger" receptors whose function is to remove modified or altered proteins, including LDL.…”

Binding and degradation of native and acetylated low density lipoproteins by monocyte derived macrophages of normal and hypercholesterolemic rabbits

“…Goldstein and co-workers (9) were the first to describe an acetic anhydride modified form of LDL that could be taken up by macrophages at a rate many times higher than that of native LDL to convert them into foam cells (12). The concentration of LDL in the intima is increased in the presence of high concentration of plasma LDL.…”