Modification of low density lipoprotein association with the arterial intima. A possible environment for the antiatherogenic action of beta-blockers.
The accumulation of lipoproteins and lipids associated with the progression of atherosclerotic lesions appears to be a sequential process involving interactions with the intimal extracellular matrix and, subsequently, with cells. Apolipoprotein B-containing lipoproteins appear first to be retained and modified focally by proteoglycans of the extracellular matrix. The association with the extracellular matrix may lead to further modifications. In vitro resident macrophages take up the modified apolipoprotein B lipoproteins via a nonsaturable mechanism that may contribute to their transformation into foam cells characteristic of the atherosclerotic lesion. The affinity of low density lipoprotein (LDL) for arterial proteoglycans in vitro is related to the charge and triglyceride content. Small, triglyceride-poor, cholesterol-rich particles interact more efficiently with proteoglycans and are taken up faster by cultured macrophages than larger triglyceride-rich ones. beta-Blockers increase the relative triglyceride content of circulating LDL, and in vitro this LDL has a lower affinity for arterial proteoglycans. These results suggest that some of the experimental antiatherogenic actions of beta-blockers may be related to a reduced LDL affinity for extracellular intima components associated with the small changes induced by the drugs in the lipoprotein structure. Hypothetically, this reduced affinity could diminish the focal accumulation of LDL in lesion-prone sites.
Camejo
G
G
Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden.
Hurt
E
E
Thubrikar
M
M
Bondjers
G
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D011509:Proteoglycans