Mechanism of lipoprotein retention by the extracellular matrix.
OBJECTIVE
Considerable evidence suggests that the subendothelial retention of atherogenic lipoproteins is a key early step in atherogenesis. In humans and experimental animals, elevated levels of plasma lipoproteins are associated with increased atherosclerosis, and lipoproteins with higher affinity for arterial proteoglycans are more atherogenic. Here we discuss the molecular mechanisms underlying lipoprotein retention in the arterial wall and how this interaction can be modulated.


RESULTS
Functional proteoglycan binding sites in lipoproteins containing apolipoprotein B have been identified and shown to have atherogenic potential in vivo. In addition to apolipoprotein B, novel bridging molecules, those that can interact with both proteoglycans and lipoproteins, have been identified that mediate the retention of atherogenic particles in the vessel wall. The interaction between lipoproteins and proteoglycans can be enhanced by the modification of lipoproteins in the circulation and in the arterial wall, by alterations in the subendothelium, and by changes in proteoglycan synthesis that result in a more atherogenic profile. The retention of atherogenic lipoproteins is a potential target for therapies to reverse atherosclerosis, and in-vitro studies have identified compounds that decrease the affinity of proteoglycans for lipoproteins.


CONCLUSIONS
Considerable progress has been made in understanding the association between lipoproteins and cardiovascular disease. This review highlights the importance of the interaction between lipoproteins and the arterial matrix.
Gustafsson
Maria
M
Wallenberg Laboratory for Cardiovascular Research and the Cardiovascular Institute, The Sahlgrenska Academy at Göteborg University, 413 45 Göteborg, Sweden. maria.gustafsson@wlab.gu.se
Borén
Jan
J
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001161:Arteriosclerosis / Q000473:pathology; D002318:Cardiovascular Diseases / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008954:Models, Biological; D011509:Proteoglycans / Q000378:metabolism
D001055:Apolipoproteins B; D008074:Lipoproteins; D011509:Proteoglycans