High-density lipoprotein atherosclerosis

Cholesterol is biosynthesized in the liver trans ported throughout the body to be used in a va riety of ways and returned to the liver where it serves as the biosynthetic precursor to other steroids But cholesterol is a lipid and isn t soluble in water How can it move through the blood if it doesn t dis solve in if The answer is that it doesn t dissolve but IS instead carried through the blood and tissues as part of a lipoprotein (lipid + protein = lipoprotein) The proteins that carry cholesterol from the liver are called low density lipoproteins or LDLs those that return it to the liver are the high-density lipoproteins or HDLs If too much cholesterol is being transported by LDL or too little by HDL the extra cholesterol builds up on the walls of the arteries caus mg atherosclerosis A thorough physical examination nowadays measures not only total cholesterol con centration but also the distribution between LDL and HDL cholesterol An elevated level of LDL cholesterol IS a risk factor for heart disease LDL cholesterol is bad cholesterol HDLs on the other hand remove excess cholesterol and are protective HDL cholesterol IS good cholesterol... 

Contrary to LDL, high-density lipoproteins (HDL) prevent atherosclerosis, and therefore, their plasma levels inversely correlate with the risk of developing coronary artery disease. HDL antiatherogenic activity is apparently due to the removal of cholesterol from peripheral tissues and its transport to the liver for excretion. In addition, HDL acts as antioxidants, inhibiting copper- or endothelial cell-induced LDL oxidation [180], It was found that HDL lipids are oxidized easier than LDL lipids by peroxyl radicals [181]. HDL also protects LDL by the reduction of cholesteryl ester hydroperoxides to corresponding hydroperoxides. During this process, HDL specific methionine residues in apolipoproteins AI and All are oxidized [182]. 

Nicholls SJ, Tuzcu EM, Sipahi 1, Grasso AW, Schoenhagen P, Hu T, Wolski K, Crowe T, Desai MY, Hazen SL, Kapadia SR, Nissen SE. (2007) Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. J Amer Med Assn 297 499-508. 

The role of the antioxidant properties of vitamins C, E, and p-carotene in the prevention of cardiovascular disease has been the focus of several recent studies. Antioxidants reduce the oxidation of low-density lipoproteins, which may play a role in the prevention of atherosclerosis. However, an inverse relationship between the intake or plasma levels of these vitamins and the incidence of coronary heart disease has been found in only a few epidemiological studies. One study showed that antioxidants lowered the level of high-density lipoprotein 2 and interfered with the effects of lipid-altering therapies given at the same time. While many groups recommend a varied diet rich in fruits and vegetables for the prevention of coronary artery disease, empirical data do not exist to recommend antioxidant supplementation for the prevention of coronary disease. 

Quig, D. W., and D. B. Zilversmit. High-density lipoprotein metabolism in a rabbit model of hyperalphalipo-proteinemia. Atherosclerosis 1989 76(1) 9-19. 

Liver toxicity is a rare side effect of CBZ therapy (Trimble, 1990), although a recent study reported that 9% of children on CBZ had mildly elevated aspartate aminotransferase (Camfield and Camfield, 1985). Higher mean serum total cholesterol (TC) levels, mean low-density lipoprotein level, and mean TC/high-density lipoprotein ratio have been reported in children with epilepsy treated with CBZ, compared with controls (Sozuer et ah, 1997). Conversely, an increase in serum high-density lipoproteins was reported in a smaller sample of patients treated with CBZ, and was therefore interpreted as a possible protective factor against atherosclerosis (Yalcin et ah, 1997). 

Asztalos BE, Brousseau ME, McNamara JR, Horvath KV, Roheim PS, Schaefer EJ (2001) Subpopulations of high density lipoproteins in homozygous and heterozygous Tangier disease. Atherosclerosis 156 217-225... 

Eckardstein Avon (2005) Differential diagnosis of familial high density lipoprotein deficiency syndromes. Atherosclerosis 186 231-239... 

The plasma lipoproteins are spherical macromolecular complexes of lipids and specific proteins (apolipoproteins or apoproteins). The lipoprotein particles include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They differ in lipid and protein composition, size, and density (Figure 18.13). Lipoproteins function both to keep their component lipids soluble as they transport them in the plasma, and also to provide an efficient mechanism for transporting their lipid contents to (and from) the tissues. In humans, the transport system is less perfect than in other animals and, as a result, humans experience a yradual deposition of lipid—especially cholesterol—in tissues. This is a potentially life-threat-en ng occurrence when the lipid deposition contributes to plaque formation, causing the narrowing of blood vessels (atherosclerosis). 

Lipid changes seen with the most widely used combined oral contraceptives comprise an increase in low density lipoprotein and reductions in high density lipoprotein and cholesterol. The third-generation products have these effects to a much smaller extent, leading to claims that they would be less likely to have long-term adverse cardiovascular effects related to atherosclerosis. However, such a claim reflects an all too readily adopted belief that the lipid changes produced by the more traditional combined oral contraceptives are in this respect capable of causing this type of (primarily arterial) cardiovascular disease. This is of itself far from certain. 

Disorders in lipoprotein metabolism are critical in the etiology of several disease states, such as coronary heart disease and atherosclerosis. Thus, there is considerable interest in the development of novel methods for the analysis of lipoprotein complexes. A simple chromatographic method for the separation of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) from intact serum or plasma has been reported recently [65]. The separation was achieved by using an hydroxyapatite column and elution with pH 7.4 phosphate buffer with lOOpl injections of whole... 

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