The Interaction of Serum and Arterial Lipoproteins with Elastin of the Arterial Intima and Its Role in the Lipid Accumulation in Atherosclerotic Plaques

Abstract

A B S T R A C T Arterial elastin appears to be a proteinlipid complex with the lipid component being bound to elastin peptide groups. In atherosclerotic lesions the lipid content of elastin increases progressively with increasing severity of atherosclerosis. The increases in the lipid content of plaque elastin are mainly due to large increases in cholesterol with about 80% of the cholesterol being cholesterol ester. This deposition of cholesterol in elastin accounts for a substantial part of the total cholesterol accumulation in atherosclerotic lesions of all stages. The present in vitro study suggests that the mechanism involved in the deposition of lipids in arterial elastin may be an interaction of the elastin protein with serum or arterial low density or very low density lipoproteins (LDL and VLDL) resulting in a transfer of lipids, but not of lipoprotein protein to the elastin. No significant lipid transfer occurred from the high density lipoproteins or chylomicrons. The amount of lipid taken up by plaque elastin was strikingly higher than by normal elastin and consisted mainly of cholesterol with over 80% of the cholesterol being cholesterol ester. The precondition for the lipid accumulation in plaque elastin appeared to be an altered amino acid composition of the elastin protein consisting of an increase in polar' amino acids and a reduction in cross-linking amino acids. Subsequent treatment of lipoprotein-incubated arterial elastin with hot alkali and apolipoproteins did not reverse the binding of lipoprotein lipid to diseased elastin. INTRODUCTIONArterial elastic membranes appear to play an important role in the development of atherosclerotic plaques (1-9).In previous autoradiographic studies after intravenous injection of [8H] cholesterol (10), dense accumulations of radioactive cholesterol occurred on the split and fragReceived for publication 11 January 1972 and in revised form 15 June 1972. mented intimo-medial elastic membranes but not over collagen depositions in atherosclerotic plaques of all stages. These plaques included very small microscopic lesions which did not contain lipid in the cells of the slightly raised intima by autoradiography or lipid staining.Recent biochemical analyses of arterial elastin preparations have shown that the lipids accumulating on elastic membranes of atherosclerotic lesions are associated with the elastin protein of these elastic membranes, even in early atherosclerosis (11). The arterial elastin preparations were defined as that protein material which remained undegraded after alkali hydrolysis of arterial tissue homogenates. The studies suggest that arterial elastin is a protein-lipid complex with the lipids being bound to the elastin peptides. The composition of this protein-lipid complex is altered in elastin of atherosclerotic plaques. As compared with normal elastin, plaque elastin has a significantly higher content of polar amino acids and a significantly lower content of cross-linking amino acids. The alteration of plaque elastin protein is associated wi...

Age-related changes in human macular Bruch's membrane as seen by quick-freeze/deep-etch

“…This may be analogous to the early pathogenesis of an arteriosclerosis that demonstrates LDL depositions in the elastic lamina of the vascular intima (Kramsch and Hollander, 1973;Guyton et al, 1985;Bocan et al, 1988;Podet et al, 1991;Bobryshev and Lord, 1999;Wang et al, 2001). It has been postulated that LDLs can interact with elastin fibrils via hydrophobic amino acids (Bobryshev and Lord, 1999) or by interactions between the oxidized LDL and calcium ion binding elastin fibrils (Wang et al, 2001).…”

Detection of HOCl-mediated protein oxidation products in the extracellular matrix of human atherosclerotic plaques

“…Oxidative damage to the ECM of the artery wall has been suggested to play a significant role in the development and progression of atherogenesis, although quantitative evidence for such oxidation is scarce, and the exact nature of the oxidized materials formed is poorly defined [12][13][14][15][16][17][18]. Furthermore, the slow rate of turnover of proteins present in the ECM, and the absence of extracellular repair or catabolic enzymes, is likely to result in the accumulation of such damage (reviewed in [41,49,50]).…”

“…It is well established that the internal elastic lamina of the artery wall is altered in human atherosclerotic plaques, with both structural modification of the lamina and the accumulation of lipids at such sites having been reported [12][13][14]. Other ECM components, including elastin and proteoglycans, are also believed to undergo fragmentation and\or physicochemical alteration during atherogenesis [12,15,16]. Elastin isolated from plaques has been reported to contain fluorophores that have been postulated to be derived from oxidized amino acids [17].…”

Effect of normolipemic and hyperlipemic serum on biosynthetic response to cyclic stretching of aortic smooth muscle cells.

“…We have shown elsewhere 27 that an elastin growth substrate increases cholesteryl ester synthesis and induces foam cell formation by smooth muscle cells in culture. Since elastin binds liplds in arteries, 28 it Is likely that a similar lipid-elastin binding occurs In vitro and that uptake of hyperlipemic LDL by smooth muscle cells is enhanced when the LDL is bound to elastin. Exposure to HLS under these conditions could also result in inhibition or deceleration of matrix fiber synthesis, for hyperilpidemic LDL has been shown to be toxic to cultured arterial smooth muscle cells 29 and may, therefore, promote cholesteryl ester accumulation in these cells 30 and suppress matrix macromolecule production.…”