Ultracentrifugal and electron microscopic studies of human serum low-density lipoprotein (LDL) and several of its derivatives led to the formulation of a model in which the 20 protein subunits, probably globular, are arranged in a dodecahedral pattern with icosahedral symmetry. In such a model the LDL surface is occupied by both protein and lipids, predominantly phospholipids, as supported by the results of the hydrolysis of LDL by phospholipase A and C. Neutral lipids (cholesterol esters and glycerides) would be in the interior of the molecule.

Adult↗

PubMed1969

Isolation and properties of lipoproteins from normal rat serum.

Three major classes of lipoproteins (VLDL, d <1.006; LDL, d 1.006-1.040; HDL, d 1.063-1.21) were isolated by ultracentrifugal flotation from the serum of normal male Sprague-Dawley rats. Their physical, chemical, and immunological properties were analyzed and compared with those of their water-soluble, essentially lipid-free derivatives. Studies were also carried out on the d > 1.21 fractions. Each product was found to have distinct characteristics, and this was also indicated by spectral analyses carried out by the techniques of circular dichroism and UV absorption spectroscopy. The results provided evidence for the mutual role of the protein and lipids in determining the structure, and perhaps the immunological specificity, of serum lipoproteins.

Acrylates↗

PubMed1965

Factors affecting lipoprotein metabolism.

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Animals↗

PubMedDate not supplied

cDNA sequence of human apolipoprotein(a) is homologous to plasminogen.

Lipoprotein(a) is an LDL-like lipoprotein whose concentration in plasma is correlated with atherosclerosis. The characteristic protein component of lipoprotein(a) is apolipoprotein(a) which is disulphide-linked to apolipoprotein B-100. Sequencing of cloned human apolipoprotein(a) complementary DNA shows that it is very similar to human plasminogen. It contains a serine protease domain and two types of plasminogen-like kringle domains, one of which is present in 37 copies.

Amino Acid Sequence↗

PubMedDate not supplied

Lipoprotein(a), fibrin binding, and plasminogen activation.

Lipoprotein(a) (Lp[a]) is a complex plasma lipoprotein in which apolipoprotein (apo) B-100 is covalently linked by a disulfide bridge to a unique apolipoprotein, apo(a). The cDNA of apo(a) has recently been isolated and sequenced, and a remarkable homology to human plasminogen has been noted. In this report, we demonstrate that, like plasminogen, Lp(a) binds to fibrin. In addition, Lp(a) competes with plasminogen and tissue-type plasminogen activator for fibrin binding. As a functional consequence of these binding properties, we show that Lp(a) attenuates the fibrin-dependent enhancement of tissue-type plasminogen activator activity against the native substrate, and does so as an uncompetitive inhibitor (Ki = 15 nM). Finally, we show that in a plasma milieu, Lp(a) attenuates clot lysis induced by tissue-type plasminogen activator. None of these effects was noted with low density lipoprotein free of apo(a). These data suggest that Lp(a) influences the fibrinolytic system and probably does so by virtue of the fibrin binding properties conferred by the kringle repeats of apo(a).

Binding, Competitive↗

PubMedDate not supplied

Structural and functional changes of rhesus serum low density lipoproteins during cycles of diet-induced hypercholesterolemia.

Over the course of a 2-year study, two male rhesus monkeys underwent episodes of diet-induced hypercholesterolemia (from a diet supplemented with 25% coconut oil and 2% cholesterol) followed by regression phases in which the animals received a low fat Purina chow diet. During the induction of hypercholesterolemia, serum cholesterol, apo B, saturation of low density lipoprotein (LDL) cholesteryl ester fatty acyl chains, and the ability of the serum to stimulate cholesterol esterification by smooth muscle cells rose immediately and in parallel, whereas there was a lag period before the serum became mitogenic to smooth muscle cells. Concurrently, there were important changes in the density, size, chemistry, and concentration of the LDL species in the rhesus serum; induced LDL shifted from the LDL-II to the LDL-I density region with increasing cholesterol concentration. Both structural and functional changes were reversed upon return to a normal Purina chow diet, although at different rates. Serum cholesterol, apo B, and the rate of cholesterol esterification in smooth muscle cells promoted by the serum declined in parallel while the mitogenicity of the serum to smooth muscle cells and the degree of saturation of LDL cholesteryl ester fatty acids took longer to return to normal values. In fact, there was an immediate and dramatic rise in saturation upon reversal before the LDL cholesteryl ester fatty acyl chains returned to their normal composition. The Lp(a) particles did not increase in either concentration or size in response to the test diet, although the change in their lipid composition was similar to those of the other LDL species. The studies indicate that dietary manipulations affect the physicochemical properties of the LDL particles, and that the resultant structural alterations are accompanied by changed in vitro cellular response, suggestive of a greater atherogenicity.

Animals↗