Cholesterol decreasing level

The receptor may recycle to the surface, the LDL is degraded, and cholesterol is released into the cell. Expression of the gene for LDL receptors (apoB-100 receptor) is r ulated by the cholesterol level within the cell. High cholesterol decreases expression of this gene. 

The important point for patients is not so much that plasma cholesterol decreases but that the clinical endpoints decrease nonfatal heart attacks, coronary artery disease deaths, surgery for coronary artery disease, and total mortality. Subsequent to the approval of statins based on reduction of plasma cholesterol levels, several large, controlled clinical trials have been carried out to establish the effects of statin use on these clinical endpoints. ... 

Decreased levels of internalized cholesterol lead to elevated activity of the chief enzyme responsible for endogenous cholesterol synthesis, HMG-CoA reductase, and consequent excessive synthesis of cholesterol. 

This effect may be due to decreasing hepatic cholesterol and cholesterol ester levels to such an extent that hepatic formation of VLDL is impaired. The statins also have been claimed to reduce blood cholesterol levels modestly in some patients with homozygous familial hypercholesterolemia, a condition often fatal in childhood or in early adulthood. 

This combination effectively controls VLDL levels during resin therapy of familial combined hyperlipoproteinemia or other disorders involving both increased VLDL and LDL levels. When VLDL and LDL levels are both initially increased, doses of niacin as low as 1-3 g/d may be sufficient in combination with a resin. The niacin-resin combination is effective for treating heterozygous familial hypercholesterolemia. Niacin also significantly elevates levels of HDL cholesterol and frequently decreases levels of Lp(a). 

VLDLs are synthesized in the liver and transport triacylglycerols, cholesterol and phospholipids to other tissues, where lipoprotein lipase hydrolyzes the triacylglycerols and releases the fatty acids for uptake. The VLDL remnants are transformed first to IDLs and then to LDLs as all of their apoproteins other than apoB-100 are removed and their cholesterol esterified. The LDLs bind to the LDL receptor protein on the surface of target cells and are internalized by receptor-mediated endocytosis. The cholesterol, which is released from the lipoproteins by the action of lysosomal lipases, is either incorporated into the cell membrane or re-esterified for storage. High levels of intracellular cholesterol decrease the synthesis of the LDL receptor, reducing the rate of uptake of cholesterol, and inhibit HMG CoA reductase, preventing the cellular synthesis of cholesterol. 

The other system controlling cholesterol biosynthesis involves both the cytosolic HMG-CoA synthase and the ER enzyme HMG-CoA reductase and is based on the cellular levels of respective mRNAs. Increasing free cholesterol decreases both enzyme activities by decreasing the levels of their mRNAs and increasing enzyme degradation processes. The half-life of HMG-CoA reductase may be as short as 1.7 h. Cellular uptake of LDL maintains cholesterol biosynthesis at a relatively low level, and this is achieved through an LDL degradation product-free cholesterol. Some authorities have maintained that hydroxylated... 

The commonly recognized risk factors for atherosclerosis include increasing age, sex (males > females until menopause, after which the incidence is similar), serum lipid levels (increased total cholesterol and low-density lipoprotein cholesterol, decreased high-density lipoprotein cholesterol, etc.), diabetes melli-tus, hypertension, and obesity. Other less well recognized but very important risk factors include increased plasma homocysteine, fibrinogen, and coagulation factor VII increased blood hematocrit, leukocyte count (increased neutrophils), and C-reactive protein and clinical depression. 

Starch mixed with such polysaccharide gums as guar, xanthan, and locust bean are used as food thickeners, especially when a surfactant is added.1055 A composition of guar gum coated with starch has been patented for decreasing levels of cholesterol and glucose in blood.1057 Starch blended with achrodextrin, gum arabic, and sodium silicate is used as an adhesive for book binding.1058... 

Dietary MUFA have been found to have several positive effects that include, in addition to lowering human LDL-cholesterol plasma levels, positive effects on lipoprotein oxidation, coagulation, and fibrinolysis (29). Low-fat, monounsaturate-rich diets reduce the susceptibility of low-density lipoproteins to peroxidation ex vivo (30). In hypercholesterolemic subjects, diets containing MUFA resulted in favorable alterations in the fatty acid composition and oxidative profile of LDL in hypercholesterolemic subjects that were characterized as an increase in lipid peroxide lag time and a decrease in lipid peroxide formation (30). In animal studies. 

The oxidation of LDL cholesterol is now recognized as a key event in atherosclerosis. Macrophages take up oxidized LDL cholesterol more readily, and this contributes to plaque formation. Soy isoflavones have been reported to inhibit oxidation by macrophages. Clinical trials have reported that consumption of 56-57 mg/day of isoflavones causes a significant increase (8-15%) in the lag time for cholesterol oxidation, and consequently decreased levels of oxidized LDL cholesterol. ... 

Although there are still some discrepancies in the hterature regarding zinc levels in dialysis patients, most studies have found decreased levels of the element in serum [64,65] and muscles whereas the levels in bone [63] and other tissues seem to be normal or even increased suggesting translocation of the element in uremia. The dialysis treatment itself seems to have little or no effect on the serum zinc concentrations. Zinc deficiency in uremic patients has been associated with anorexia, disturbances in taste and sexual performance [66] whereas decreased plasma zinc seem to correlate with erythrocyte superoxide dismutase levels [67]. As evaluated by Tiirk et al. [68], zinc supplementation did not have any effect on the restoration of immune parameters or enhancement of the antibody response to multivalent influenza vaccine in hemodialysis patients. On the ofher hand however, has zinc supplementation been reported an effective means of improving serum levels of zinc and cholesterol in the hemodialysis patient [69]. 

HDL-cholesterol levels significantly decreased in APOE-3/3 (p<0.001) > APOE-3/4 (p< 0.05), with no significant changes in patients with other genotypes. In contrast, LDL-cholesterol levels showed identical changes to those observed in total cholesterol, with similar differences among genotypes at baseline and almost identical decreased levels after treatment (APOE-3/3,... 

Studies of cells in culture have provided considerable information about the control of this pathway [97]. In early studies, cultured skin fibroblasts were maintained for 24 h in a medium containing lipoprotein-deficient serum. These cells showed increased binding of LDL to cell surface receptors and increased HMG-CoA reductase activity. When LDL were added to the medium, binding, uptake, and degradation of the LDL followed. LDL CE were hydrolyzed, and decreased levels of both HMG-CoA reductase and the apo B/E receptor were seen. Furthermore, increased formation of cholesteryl oleate could be demonstrated. In subsequent studies, modified LDL with a net positive charge were used. These cationized LDL were internalized by a mechanism that did not depend on the apo B/E receptor, and that led to a substantial increase in cell cholesterol [103]. Under these conditions there was again increased synthesis of cholesteryl oleate. These findings support two principal conclusions (1) plasma lipoprotein CE is an important source of cholesterol for fibroblasts and similar cells and (2) the formation of intracellular... 

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