Modified serum lipoproteins

Anon. Regular or decaf/ Coffee consumption and serum lipoproteins. Nutr Rev 1992 50(6) 175-178. Hasegawa, R. and N. Ito. Liver medium-term bioassay in rats for screening of carcinogens and modifying factors in hepatocarcingenesis. Food Chem Toxicol 1992 30(11) 979-992. 

From the foregoing it is natural that treatments designed to modify plasma lipoprotein concentrations have been sought with vigour. In particular, the aim of reducing serum cholesterol and LDL concentrations has been to induce a decrease in the cholesterol content and size of atheromatous lesions... 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

Lipoprotein disorders are detected by measuring lipids in serum after a 10-hour fast. Risk of heart disease increases with concentrations of the atherogenic lipoproteins, is inversely related to levels of HDL, and is modified by other risk factors (Table 35-1). Evidence from clinical trials suggests that LDL cholesterol levels of 60 mg/dL may be optimal for patients with coronary disease. Ideally, triglycerides should be below 120 mg/dL. Differentiation of the disorders requires identification of the lipoproteins involved (Table 35-2). Diagnosis of a primary disorder usually requires further clinical and genetic data as well as ruling out secondary hyperlipidemias (Table 35-3). 

Numerous animal and human studies suggest that dietary cholesterol and certain saturated fatty acids increase serum as well as LDL-cholesterol concentrations. Even though humans with elevated serum cholesterol levels may be at risk, evidence also is mounting to suggest that the complicated processes that occur during atherosclerosis involve not only the participation of modified lipoproteins, but also low level and chronic inflammation and related disorders of the immune... 

Sugiuchi H, Uji Y, Okabe H, Me T, Uekama K, Kayahara N, Miyauchi K. Direct measurement of high-density lipoprotein cholesterol in serum with polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin. Clin Chem 1995 41 717-23. 

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... 

We selected Pseudomonas pictorum (ATCC 23328) as another model system because it can degrade cholesterol. The standard encapsulation method does not result in a high-porosity membrane that would allow lipoprotein-cholesterol to cross. Therefore, we devised a modified method to prepare high-porosity agar microspheres. There was no evidence of leakage of the enclosed bacteria. Open pore agar beads were incubated in serum, and the bacterial action did not significantly... 

In addition, an epidemiological study of 1931 selected men in Finland has indicated that increases in stored iron levels, as assessed by serum ferritin concentration, is a risk factor for coronary heart disease [60]. Iron mobilized from ferritin generates reactive oxygen radicals that presumably oxidatively modify low-density lipoproteins, thereby enhancing the risk of ischemic heart disease. 

In TNCl rat astrocytes grown in Dulbecco s modified Eagle s medium + 10% fetal bovine serum, oxidised low density lipoprotein caused a dose-dependent increase in 2,7-dichlorofluorescin fluorescence, which was inhibited by pre-treatment with antioxidants, consistent with the formation of reactive oxygen species (Keller et al. 1999). 

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