Atherosclerosis phospholipids

HDL concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDLj concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDL, (HDLj) is found in... 

Cassel, D.L., et al., "The Conformation of Apolipoprotein E Isoforms in Phospholipid Complexes and Their Interaction with Human Hep G2 Cells," Atherosclerosis, 52, 203-218 (1984). 

The primary developmental mechanism of the atherosclerotic process is not completely understood. It seems likely that the development of atherosclerosis is preceded by metabolic abnormalities of the synthesis, transport, and utilization of lipids. Lipids such as triglycerides and cholesterol esters are circulated in the blood in the form of particles (lipoproteins) wrapped in hydrophilic membranes that are synthesized from phospholipids and free cholesterol. Cholesterol is transported by particles of various sizes synthesized from triglycerides, cholesterol esters, and phospholipids, each of which plays a very specific role. 

Leitinger N. (2003). Oxidized phospholipids as modulators of inflammation in atherosclerosis. Curr. Opin. Lipidol. 14 421 130. 

C3. Calvert, G. D., and Abbey, M., The isolation and partial characterisation of two lipid transfer proteins (LTP-I and LTP-II), each of which facilitates the transfer of esterified cholesterol, triglyceride and phospholipid between plasma lipoproteins. In "Atherosclerosis VI, Proceedings of the Sixth International Symposium (F. G. Schettler, A. M. Gotto, G. Middelhoff, A. J. R. Habenicht, and K. R. Jurutka, eds.), pp. 428-431. Springer-Verlag, Berlin, 1983. 

Primary targets for attack by oxygen-derived free radical species are the polyunsaturated fatty-acid (PUFA) moieties of membrane phospholipids. Attack on low-density lipoprotein PUFA (LDL PUFA) must also be considered and is of primary importance in the consideration of the aetiology of atherosclerosis. The mechanism of all such peroxidation processes is likely to be the same and the inhibitory effect of antioxidants toward PUFA can be considered to be... 

Q8 In type 1 diabetes, because of a lack of insulin, a high level of triglyceride is stored in the liver and can subsequently be converted to phospholipids and cholesterol. Hepatocytes synthesize VLDLs, which can be converted to other types of lipoproteins. These lipoproteins are major sources of cholesterol and triglycerides for most other tissues. They leave the liver, enter the blood and can result in rapid development of vascular atherosclerosis. Increased levels of atherogenic oxidized low-density lipoproteins (LDLs) are seen in hyperglycaemic individuals and contribute to macrovascular disease, which is a complication of diabetes mellitus. 

Lipoprotein associated phospholipase A2(LpPLA2> is a serine dependent lipase of novel structure which is associated with the presence of LDL in plasma. It hydrolyses oxidised phospholipids to generate lysophosphatidylcholine and oxidised free fatty acids (Scheme 1), both of which are potent chemoattractants for circulating monocytes. Accumulation of lysophosphatidylcholine results in macrophage proliferation and the endolithial dysfunction observed in patients with atherosclerosis. Inhibition of LpPLA2 would thus be expected to stop plaque build-up and provide an attractive strategy in the treatment of atherosclerosis. 

Lecithin plays an important role in the transport of fats and cholesterol from the liver to sites where they can be either used or stored. Since fats do not dissolve in water solutions like blood plasma, they are transported in spherical particles called lipoproteins. These particles can mix with water solutions because the water-friendly proteins, cholesterol and phospholipids are on the outside surface. The nonpolar fats associated with them make up the core, which is unexposed to water. Because lecithin is required for lipoprotein synthesis, a lecithin deficiency results in fats accumulating in the liver and leads to liver damage. Lecithin deficiency also leads to increased amounts of cholesterol in the blood and atherosclerosis, a disease in which narrowing of the arteries is caused primarily by the deposit of fats from the bloodstream. 

We isolated the LDL fraction from plasma of patients with atherosclerosis who had been on probucol (daily dose 250 mg) for 3 months and oxidized this probucol-contained LDL by C-15 animal lipoxygenase in vitro [31]. After decomposition of enzymatically accumulated acyl-lipohydroperoxides in LDL phospholipids by hemin with corresponding... 

Abstract. The significance of free radical oxidation of phospholipids in tissues of animals with experimental atherosclerosis was investigated. By using modem physico-chemical methods an elevated content of polyunsaturated fatty acids and other lipids peroxides was discovered in the blood and the aorta of rabbits with experimental atheromatosis. The human blood demonstrated a low level of protective enzymatic systems and a high content of products secondary to peroxidal oxidation of the lipids. The mechanism accounting for the action of lipids peroxides on the vascular wall resulting in the formation of atheromatous plaques is considered. 

Abstract. When experimental animals are kept on an atherogenic diet the NADPH-dependent phospholipid deoxygenase in the membranes of the hepatic endoplasmic reticulum is activated and the degree of membrane oxidation is increased. Peroxide modification of microsomal membranes is attended by changes in their conformation and as a consequence, changes in the activity of membrane-bound enzymes. Proceeding from the fact that the synthesis of the components and the assembly of the supramolecular lipoprotein structure as well as cholesterol catabolism are accomplished by the enzyme systems localized in the hepatic microsomes, the role of peroxidation of the microsomal lipids in the pathogenesis of atherosclerosis is discussed. 

Jiang XC, Qin S, Qiao C, Kawano K, Lin M, Skold A, Xiao X, Tall AR (2001) Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency. Nat Med 7 847-852... 

Krauss RM (2010) Phospholipid transfer protein and atherosclerosis genetic studies take aim at a moving target. Circulation 122 452 54... 

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