Evidence that lysolecithin is an important causal agent of atherosclerosis.
We examine the hypothesis of Portman et al. (1970) that lysolecithin is a causal agent of atherosclerosis. Four lines of argument support this hypothesis. (1) Lysolecithin is present, taken up and can act. Large amounts of lysolecithin are formed in plasma concomitant with triglyceride transport and it is readily taken up by arteries and retained for some time. Lysolecithin in aortic intima increases several-fold early in the induction of atherosclerosis in animals. From model system studies it is plausible that physiological doses of lysolecithin have physiologically significant effects. (2) At least one plausible mechanism of action can be formulated: stimulation of smooth muscle cell division due to lysolecithin-increased Ca2+ uptake. (3) The hypothesis is consistent with, and rationalizes, many literature observations in that inferred lysolecithin levels or production rates are appropriately correlated with a variety of positive and negative risk factors to a degree highly unlikely by chance. We found no data contradicting the hypothesis and only one piece weakening it. (4) A mechanism is outlined showing that low density lipoprotein receptor deficiency, the severest known risk factor, should cause the delivery of very high lysolecithin doses to artery walls. We conclude that the evidence, although indirect, is strong enough to give direct tests a high priority.
D000818:Animals; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology*; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000009:adverse effects / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008244:Lysophosphatidylcholines / Q000097:blood / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D008954:Models, Biological; D011817:Rabbits; D051381:Rats; D012306:Risk
D002791:Cholesterol, Dietary; D008244:Lysophosphatidylcholines; D008563:Membrane Lipids; D002118:Calcium