Lipid metabolism disorders represent a critical cardiovascular risk factor. Epidemiological data, in vivo and in vitro studies have contributed to delineating the role of lipids in atherosclerosis. In particular, lipids and the lipoproteins that mediate their transport are differently implicated in the atherogenic process (Table 1).
Table1. Role of lipoproteins in atherosclerosis
Chylomicrons are large molecules and, since they cannot penetrate the artery walls, they are not involved in the development of atherosclerosis. On the contrary, LDLs contribute to the development of atherosclerosis by dam aging the endothelium, the first stage of the atherosclerotic process, and by accumulating in the intima of the artery, thus inducing the formation and growth of the atheromatic plaque.
The Lp(a), due to its peculiar intermediate composition between LDL and plasminogen, may contribute to the development of atherosclerosis and/or thrombosis. Indeed, like LDL, Lp(a) can accumulate in the arterial wall, promoting those initial processes of atherosclerosis, such as inflammation and the formation of foamy cells, which lead to the genesis of the atheromatic plaque. Moreover, since a part of the molecule possesses a sequence similar to plasminogen, it contributes to the formation of the clot through the inhibition of endogenous fibrinolysis, competing with plasminogen for the binding on the endothelial surface; the final result is an increased risk of thrombus formation which leads to the occlusion of the vessel.
HDLs, on the other hand, have a protective role against atherosclerosis, which they perform through multiple functions. Among these, the best known is the reverse transport of cholesterol and, in particular, the ability of HDL to mobilize excess cholesterol from macrophages in the arterial wall. In this way, HDLs reduce the accumulation of cholesterol- laden foam cells within the arterial wall, a phenomenon that constitutes one of the earliest stages in the pathogenesis of atherosclerosis. Moreover, HDLs exert their antiatherogenic role through other mechanisms, such as the prevention of LDL oxidation, anti-inflammatory effects, prevention of vascular endothelial cell apoptosis, profibrinolytic, and antithrombotic effects.
