High Density Lipoproteins and Atherosclerosis

Miller, GJ

doi:10.1146/annurev.me.31.020180.000525

Cited by 165 publications

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“…LCAT functions in connection with the HDL and seems to participate in the transfer of cholesterol between tissues and lipoproteins (16,17). An elevated serum level of LDL and very low density lipoprotein (VLDL) and/or low concentration of HDL have been considered to increase the ac cumulation of the cholesterol in the arterial wall (18,19). In the present study, LDL-TC plus VLDL-TC levels (considered as the difference between serum TC and HDL-TC) were increased, while the HDL-TC level was decreased in the mice fed the high-cholesterol diet.…”

Section: Discussionmentioning

confidence: 50%

Cholesterol metabolism in serum and aorta of inbred mice fed a high-cholesterol diet.

et al. 1984

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Abstract-Biochemical characterization of the serum and aorta in inbred C57BL/ 6Cr mice fed a high-cholesterol diet was investigated by determining the total cholesterol (TC) and free cholesterol (FC) levels in serum, high density lipoprotein (HDL) and aorta.Serum lecithin:cholesterol acyltransferase (LCAT) activity was also determined.A modified fluoroenzymatic method for microdetermination of cholesterol was successfully used. TC and FC levels of the aorta in the mice were significantly increased by the high-cholesterol diet. Serum TC and FC levels of mice fed the high-cholesterol diet were increased about 80% and 110%, respectively, compared with the control.On the other hand, both HDL-TC and HDL-FC levels were decreased about 50%. The HDL-TC/serum-TC ratio was markedly decreased, while the atherogenic index was markedly increased with the high-cholesterol diet. LCAT activity was also strikingly decreased.

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Section: Discussionmentioning

confidence: 50%

Cholesterol metabolism in serum and aorta of inbred mice fed a high-cholesterol diet.

et al. 1984

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“…Key Words: transgenic mice Ⅲ hypertriglyceridemia Ⅲ cholesterol Ⅲ lipoproteins Ⅲ atherosclerosis P lasma lipoproteins influence the development of atherosclerosis, and their concentrations are associated with the risk of coronary heart disease. 1 The genes for 3 apolipoproteins, apoA-I, apoC-III, and apoA-IV, are grouped together in a cluster on 17 kb of human chromosome 11. 2 ApoA-I is the major protein component of HDL.…”

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confidence: 99%

Expression of Human Apolipoprotein A-I/C-III/A-IV Gene Cluster in Mice Induces Hyperlipidemia but Reduces Atherogenesis

Vergnes

Baroukh

Ostos

et al. 2000

ATVB

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Abstract-The apolipoprotein (apo)A-I/C-III/A-IV gene cluster is involved in lipid metabolism and atherosclerosis.Overexpression of apoC-III in mice causes hypertriglyceridemia and induces atherogenesis, whereas overexpression of apoA-I or apoA-IV increases cholesterol in plasma high density lipoprotein (HDL) and protects against atherosclerosis. Each gene has been studied alone in transgenic mice but not in combination as the entire cluster. To determine which phenotype is produced by the expression of the entire gene cluster, transgenic mice were generated with a 33-kb human DNA fragment. The results showed that the transgene contained the necessary elements to direct hepatic and intestinal expression of the 3 genes. In the pooled data, plasma concentrations were 257Ϯ9, 7.1Ϯ0.5, and 1.0Ϯ0.2 mg/dL for human apoA-I, apoC-III, and apoA-IV, respectively (meanϮSEM). Concentrations of these apolipoproteins were higher in males than in females. Human apoA-I and apoC-III concentrations were positively correlated, suggesting that they are coregulated. Transgenic mice exhibited gross hypertriglyceridemia and accumulation of apoB 48 -containing triglyceride-rich lipoproteins. Plasma triglyceride and cholesterol concentrations were correlated positively with human apoC-III concentration, and HDL cholesterol was correlated with apoA-I concentration. In an apoE-deficient background, despite being markedly hypertriglyceridemic, cluster transgenic animals compared with nontransgenic animals showed a 61% reduction in atherosclerosis. This suggests that apoA-I and/or apoA-IV can protect against atherosclerosis even in the presence of severe hyperlipidemia. These mice provide a new model for studies of the regulation of the 3 human genes in combination. Key Words: transgenic mice Ⅲ hypertriglyceridemia Ⅲ cholesterol Ⅲ lipoproteins Ⅲ atherosclerosis P lasma lipoproteins influence the development of atherosclerosis, and their concentrations are associated with the risk of coronary heart disease. 1 The genes for 3 apolipoproteins, apoA-I, apoC-III, and apoA-IV, are grouped together in a cluster on 17 kb of human chromosome 11. 2 ApoA-I is the major protein component of HDL. Through its ability to promote cholesterol efflux from cultured cells and to activate lecithin:cholesterol acyltransferase (LCAT), it is involved in reverse cholesterol transport (RCT). 1 Expression of the human apoA-I ( h apoA-I) gene decreases the development of fatty lesions in cholesterol-fed transgenic (Tg) mice 3 and in apoE-deficient (apoE Ϫ/Ϫ ) mice. 4 ApoA-I deficiency in mice did not increase atherogenesis in a normal background 5 but did so in hypercholesterolemic mice expressing human apoB. 6 ApoC-III is a component of HDL and triglyceride-rich lipoproteins (TGRLs). Plasma apoC-III concentration is positively correlated with triglyceride concentration. By inhibiting TGRL catabolism, apoC-III induces hypertriglyceridemia in Tg mice. 7 Expression of the gene was not atherogenic in apoE Ϫ/Ϫ mice. 8 In contrast, h apoC-III expression, in normal or in LDL ...

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“…Alkaline phosphatase-conjugated goat antifrom Sigma Chemical Co. (St. Louis, MO). It gave a single rabbit IgG (Fab ) 2 , at a 1:2,000 dilution for 1 hour at RT, band of approximately 28 kd on sodium dodecyl sulfate poly-served as the second antibody. After the final washing, blots acrylamide gel electrophoresis (SDS-PAGE), with a purity were visualized with NBT-BCIP.…”

Section: Methodsmentioning

confidence: 99%

“…After three rinses, the amount of bound Apo ring Diagnostics Inc. (Sommerville, NJ). Alkaline phospha-A-I or acetaldehyde-modified Apo A-I was quantified by meatase-conjugated goat anti-rabbit immunoglobulin (Ig)G suring the colored reaction product (1 mg/mL p-nitrophenyl (Fab ) 2 , low-molecular-weight markers, and nitrocellulose phosphate in 10 mmol/L diethanolamine containing 0.5 membranes were from Bio-Rad Lab (Richmond, CA). Acetal-mmol/L MgCl 2 ).…”

Section: Binding Assay Of Apo A-i and Acetaldehyde-modified Apomentioning

confidence: 99%

Binding of apolipoprotein A-I and acetaldehyde-modified apolipoprotein A-I to liver extracellular matrix

et al. 1996

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Apolipoprotein A-I (Apo A-I), a protein producedApolipoprotein A-I (Apo A-I), a 28-kd protein, is synmainly by hepatocytes, is decreased in the sera of alco-thesized mainly by hepatocytes. It is the major protein holic patients with liver fibrosis and cirrhosis. To ex-of the high-density lipoproteins. These particles are inplain this decrease, we investigated possible interac-volved in the reverse transport of cholesterol, a process tions between liver extracellular matrix (ECM) and Apo that promotes cholesterol efflux from cells to the liver. 1 A-I. Using a solid-phase binding assay, we evaluated the Apo A-I is a marker of atheromatous disease, and its binding of Apo A-I to the different liver matrix compo-decrease in serum is correlated with a higher risk of The mechanisms of serum Apo A-I decrease in liver urable. Apo A-I bound also to ECM in vivo because Apo fibrosis are unknown, but it has been shown that serum A-I was detected by immunofluorescence on fibrous Apo A-I measurement alone 4 or in correlation with septa in liver biopsy specimens of alcoholic patients. Be-other biological data such as prothrombin time and gcause a negative correlation between Apo A-I and liver glutamyl transferase (PGA score) 5 can serve as a fibrosis is amplified in alcoholic patients, we investi-marker of liver fibrosis and cirrhosis in alcoholic pa- argument is that lipoproteins can be extracted from vessels only in association with constituents of the ECM. 8 The ECM is a multimolecular complex that forms a network between cells, and expansion of the ECM is Abbreviations: Apo A-I, apolipoprotein A-I; ECM, extracellular matrix; the hallmark of fibrosis. In the liver, the matrix is made SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; FN, up of proteins, glycoconjugates, and carbohydrate polyfibronectin; C, collagen; Ig, immunoglobulin; BSA, bovine serum albumin; mers. 9 Because of its multiple components and their EDTA, ethylenediaminetetraacetic where they are stored. [13][14][15] Copyright ᭧ 1996 by the American Association for the Study of Liver Acetaldehyde, the first oxidative metabolite of ethaDiseases.

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High Density Lipoproteins and Atherosclerosis

Cited by 165 publications

References 0 publications

Cholesterol metabolism in serum and aorta of inbred mice fed a high-cholesterol diet.

Cholesterol metabolism in serum and aorta of inbred mice fed a high-cholesterol diet.

Expression of Human Apolipoprotein A-I/C-III/A-IV Gene Cluster in Mice Induces Hyperlipidemia but Reduces Atherogenesis

Binding of apolipoprotein A-I and acetaldehyde-modified apolipoprotein A-I to liver extracellular matrix

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