Abstract
Local and focal retention of lipoproteins rather than increased influx appears to be the basis for lipoprotein deposition in arterial tissue during atherogenesis. Binding of low density lipoproteins to arterial chondroitin sulphate rich proteoglycans is mediated by specific hydrophilic peptide sequences in apoB, characterized by a high frequency of basic amino acids. One of these sequences is considered to be involved in the interaction between the lipoproteins and the LDL receptor. Consequently, it might be postulated that the receptor-mediated cellular uptake of LDL could be inhibited in the presence of an excess of arterial proteoglycans. However, LDL which has been precipitated by proteoglycan and subsequently resolubilized is taken up more avidly than native LDL both in macrophages and in smooth muscle cells. This appears to be due to a selection by the proteoglycans of a more reactive fraction of LDL. This fraction has a smaller size and less surface phospholipids. As smaller LDL particles also have a higher transfer rate into the arterial tissue they may be particularly atherogenic. Low density lipoproteins appear to be taken up with higher affinity by arterial macrophages than by smooth muscle cells. The selective transfer of the LDL to macrophages can be inhibited by alpha-tocopherol suggesting that oxidative modification may be involved in this process. In fact, binding of LDL to arterial proteoglycans also appears to increase the susceptibility of the lipoproteins to oxidative modification, as well as the susceptibility to proteolytic degradation. Thus, the interaction of LDL with proteoglycans might be involved in several of the key elements of the atherogenic process.
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Bondjers, G., Camejo, E.H., Wiklund, O., Olsson, U., Olofsson, SO., Camejo, G. (1991). The Molecular Basis for Lipoprotein Interaction with Vascular Tissue. In: Gotlieb, A.I., Langille, B.L., Fedoroff, S. (eds) Atherosclerosis. Altschul Symposia Series, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3754-0_19
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DOI: https://doi.org/10.1007/978-1-4615-3754-0_19
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