Identification of lipoproteins of intestinal origin in human atherosclerotic plaque

Abstract

Apolipoproteins (apo) B48 and B100 are exclusive markers of lipoproteins derived from the intestine and liver, respectively. Lipoproteins of hepatic origin are causally related to atherosclerosis and are found in plaque. However, lipoproteins of intestinal origin have not previously been reported in human atherosclerotic tissue, although studies in animal models suggest that chylomicrons may contribute to arterial cholesterol entrapment. In this study, we report on the relative distribution of both apoB48 and apoB100 in human atherosclerotic tissue. Lipoproteins were isolated from human femoral and carotid endarterectomy samples, from varicose vein and aortic aneurysms. ApoB was determined by Western blot analysis and quantified based on the signal to apoB48 and apoB100 protein standards of known mass. ApoB48 and apoB100 were found in human carotid and femoral endarterectomy samples, but not in varicose vein or aortic aneurysm tissue. The level of apoB48 relative to hepatic lipoproteins (B100) was found to be much greater than would be predicted based on the relative plasma concentration and arterial exposure of the two lipoprotein groups. Intimal association was substantially greater in carotid endarterectomy samples compared to femoral, however, the ratio of chylomicrons to hepatic lipoproteins was greater in the latter. On the basis that chylomicron apoB48 was found in human atherosclerotic tissue and that each chylomicron particle contains substantial quantities of cholesterol, it is possible that the contribution of intestinal lipoproteins to atherosclerosis may be significant.