Corticotropin-induced reduction of plasma lipoprotein(a) concentrations in healthy individuals and hemodialysis patients: Relation to apolipoprotein(a) size polymorphism

Arnadottir, Margret; Berg, Anna‐Lena; Kronenberg, Florian; Lingenhel, Arno; Hugosson, Therése; Hegbrant, Jörgen; Nilsson‐Ehle, Peter

doi:10.1016/s0026-0495(99)90083-5

Cited by 13 publications

(8 citation statements)

References 27 publications

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“…Our previous studies have shown that ACTH also decreases plasma Lp(a) concentration (2,3). Lp(a) is composed of an LDL particle, which also contains apo(a).…”

Section: Figmentioning

confidence: 98%

“…In the present study we found that ACTH had no effect on SR-BI mRNA in liver cells. In another series of experiments 2 we pretreated rats with ACTH and then injected radioactive labeled LDL. There were no differences in LDL clearance or LDL tissue distribution in ACTH-treated rats compared with control rats.…”

Section: Figmentioning

confidence: 99%

“…ApoE is present in all lipoprotein classes and plays a central role in lipoprotein catabolism because of its high affinity to lipoprotein receptors (36). In the rabbit, intravenous injection of apoE was associated with 2 Manuscript in preparation. a transient lowering of plasma cholesterol concentrations (37), an effect that did not involve an up-regulation of LDL-R activity (38).…”

Section: Figmentioning

confidence: 99%

“…ACTH has also been shown to influence plasma lipid and lipoprotein metabolism (2-7). Thus, we have demonstrated previously that ACTH treatment markedly and consistently lowers plasma concentrations of low density lipoproteins (LDL), very low density lipoprotein (VLDL), and lipoprotein(a) (Lp(a)) in healthy individuals (2,7), in steroid-treated patients with renal disease, and in uremic patients treated by hemodialysis (3,4). In some of the studies, an increased high density lipoprotein (HDL) cholesterol concentration was also observed (4,6).…”

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confidence: 95%

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ACTH Decreases the Expression and Secretion of Apolipoprotein B in HepG2 Cell Cultures

Xu¹,

Ekström²,

Nilsson‐Ehle³

2001

Journal of Biological Chemistry

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Administration of adrenocorticotropic hormone (ACTH)has been shown to decrease plasma concentrations of apolipoprotein B (apoB) containing lipoproteins, including lipoprotein(a), in man. However, the mechanism behind this hypolipidemic effect is unknown. This study aimed at distinguishing between the main possibilities (increased elimination or decreased production of lipoproteins) using HepG2 cell cultures. Addition of ACTH to the cell culture medium selectively downregulated apoB mRNA expression and apoB secretion in a dose-dependent manner. At 100 pmol/liter ACTH, the apoB mRNA level was about 40% lower than in the untreated cells, and the secretion of apoB into the medium was decreased to a similar extent. The expression and secretion of other apolipoproteins (apoA-I, apoE, and apoM), however, were not affected by ACTH. Under normal culture conditions the level of secretion of apoB from HepG2 cells is quite low. In the presence of 0.4 mmol/liter oleic acid secretion of apoB increased 3-fold, but this phenomenon was not seen in ACTH-treated cells. Binding and internalization of radiolabeled low density lipoprotein (LDL) by HepG2 cell, as well as LDLreceptor mRNA and scavenger receptor B-I mRNA levels, were not influenced by ACTH. In conclusion, ACTH directly and selectively down-regulated the production and secretion of apoB in HepG2 cell cultures, suggesting that a principal mechanism behind the cholesterollowering effect of ACTH in vivo may be a decreased production rate of apoB-containing lipoproteins from the liver. It is well documented that adrenocorticotropic hormone (ACTH)1 regulates important aspects of lipid metabolism in the adrenal gland, especially those related to steroid hormone homeostasis (1). ACTH has also been shown to influence plasma lipid and lipoprotein metabolism (2-7). Thus, we have demonstrated previously that ACTH treatment markedly and consistently lowers plasma concentrations of low density lipoproteins (LDL), very low density lipoprotein (VLDL), and lipoprotein(a) (Lp(a)) in healthy individuals (2, 7), in steroid-treated patients with renal disease, and in uremic patients treated by hemodialysis (3, 4). In some of the studies, an increased high density lipoprotein (HDL) cholesterol concentration was also observed (4, 6). The effects of ACTH on LDL and Lp(a) levels seem attributable to ACTH as such, because they are clearly distinct from the effects of equipotent doses of corticosteroids (6).The mechanisms behind the lipid-lowering effects of ACTH are not known. Previous data indicated that ACTH could increase LDL receptor (LDL-R) activity in HepG2 cells (6), suggesting that an increased elimination rate of LDL might be involved. It has also been reported that ACTH increased the receptor-mediated uptake of native LDL but not of oxidized LDL or of LP(a) in HepG2 cells. However, because the elimination of LDL and Lp(a) from the circulation occurs via distinctly different routes (i.e. Lp(a) does not utilize the LDL-R pathway), the parallel decrease in plasma LDL and Lp(a) concentrati...

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“…Our previous studies have shown that ACTH also decreases plasma Lp(a) concentration (2,3). Lp(a) is composed of an LDL particle, which also contains apo(a).…”

Section: Figmentioning

confidence: 98%

Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 95%

See 2 more Smart Citations

ACTH Decreases the Expression and Secretion of Apolipoprotein B in HepG2 Cell Cultures

Xu¹,

Ekström²,

Nilsson‐Ehle³

2001

Journal of Biological Chemistry

Self Cite

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“…The administration of corticotropin or its analogues (e.g. synacthene) leads to a distinct decrease of Lp(a) [2,[152][153][154], both in healthy individuals and in patients with terminal renal failure and hemodialysis and in patients after kidney transplantation. With regard to diabetes mellitus there exists a whole range of partly contradictory publications.…”

Section: Hormonal Influence On the Lp(a) Plasma Concentrationmentioning

confidence: 99%

Lipoprotein(a) - Structure, Epidemiology, Function and Diagnostics of a Cardiovascular Risk Marker

Siekmeier¹,

Scharnagl²,

Kostner³

et al. 2008

TOCCHEMJ

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Decades after its first description by Berg 1963 lipoprotein(a) (Lp(a)) is an established risk marker of cardiovascular diseases which is independent from other risk markers. The main difference of Lp(a) compared to LDL is the apo(a) residue which is covalently bound to apoB. Apo(a) is a glycoprotein which underlies a large genetic polymorphism. The latter is caused by a variation of the kringle-IV-type-2 repeats of the protein which is characterized by a large structural homology to plasminogen. The Lp(a) plasma concentration in the population is highly skewed and determined to more than 90 % by genetic factors. In healthy subjects the Lp(a)-concentration is correlated to its synthesis and not to its metabolism. Plasma concentrations of Lp(a) are affected by different diseases (e.g. diseases of liver and kidney), hormonal factors (e.g. sexual steroids, glucocorticoids, thyroid hormones), individual and environmental factors (e.g. age, cigarette smoking) as well as pharmaceuticals (e.g. derivatives of nicotinic acid) and therapeutic procedures (lipid apheresis). However, even though a large number of studies on Lp(a) were performed up to now many details of its physiological function and regulation of plasma concentration are not yet understood. In addition, studies showed contradictory results because there were large differences of the included patients, use of not sufficiently validated tests as well as analysis of frozen samples. Aim of our review was to describe function and physiological regulation of Lp(a) as well as factors influencing its plasma concentration.

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Lipids and atherosclerosis

Wanner¹

2004

Replacement of Renal Function by Dialysis

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Corticotropin-induced reduction of plasma lipoprotein(a) concentrations in healthy individuals and hemodialysis patients: Relation to apolipoprotein(a) size polymorphism

Cited by 13 publications

References 27 publications

ACTH Decreases the Expression and Secretion of Apolipoprotein B in HepG2 Cell Cultures

ACTH Decreases the Expression and Secretion of Apolipoprotein B in HepG2 Cell Cultures

Lipoprotein(a) - Structure, Epidemiology, Function and Diagnostics of a Cardiovascular Risk Marker

Lipids and atherosclerosis

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