Effectiveness of mevinolin on plasma lipoprotein concentrations in type II hyperlipoproteinemia

Hoeg, Jeffrey M.; Maher, Martha B.; Zech, Loren A.; Bailey, Kent R.; Gregg, Richard E.; Lackner, Karl J.; Fojo, S S; Anchors, Michael; Bojanovski, Marina; Sprecher, Dennis L.; Brewer, H. Bryan

doi:10.1016/0002-9149(86)90733-2

Cited by 86 publications

(20 citation statements)

References 16 publications

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“…Another potential implication of our results relates to the mechanism whereby certain drugs increase the plasma levels of HDL and apoA-I [21]. Drugs like lovastatin and niacin, by up-regulating the LDL receptor lead to increased uptake of LDL which could then be followed by an increase in apoA-I mRNA levels and, consequently, by an enhanced synthetic rate of apoA-I and HDL.…”

Section: Letters January 1989mentioning

confidence: 79%

Effect of low density lipoproteins, high density lipoproteins, and cholesterol on apolipoprotein A‐I mRNA in Hep G2 cells

et al. 1989

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We have utilized the human hepatoceUular carcinoma cell line, Hep G2, to study the effects of low density iipoproteins (LDL), high density lipoproteins (HDL), and free cholesterol on apolipoprotein (apo) A-I mRNA levels. Incubation of the Hep G2 cells with LDL and free cholesterol led to a significant increase in the cellular content of cholesterol without any effect on the yield of total RNA or in the cellular protein content. Our studies established that incubation with LDL or free cholesterol increased the relative levels of apoA-I mRNA in the Hep G2 cells. In contrast with cholesterol loading, HDL had the effect of lowering the levels of apoA-I mRNA. These results indicate the LDL and HDL pathways as well as intracellular cholesterol may be important in apoA-I gene expression and regulation.HDL; Apolipoprotein A-I

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Section: Letters January 1989mentioning

confidence: 79%

Effect of low density lipoproteins, high density lipoproteins, and cholesterol on apolipoprotein A‐I mRNA in Hep G2 cells

et al. 1989

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“…The dose of mevinolin that was required to lower the cholesterol and increase the receptor mRNA level is much higher than the dose that lowers cholesterol in humans (2,(4)(5)(6). The reason why animals such as hamsters and rabbits are relatively resistant to the effects of mevinolin is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…In hamsters and rabbits mevinolin produced a decrease in all classes of cholesterol-carrying lipoproteins, including HDL, whereas in humans mevinolin produces a selective decrease in LDL and perhaps IDL levels, without lowering HDL (4)(5)(6). This difference may be due to the relative abundance of apolipoprotein E in the HDL fractions from the lower animal species as compared with humans.…”

Section: _mentioning

confidence: 98%

“…In dogs these drugs lower the concentration of all cholesterolcarrying lipoproteins in plasma (3). In humans these drugs selectively reduce low density lipoprotein (LDL) (4)(5)(6). One mechanism for the cholesterol-lowering effect involves an increase in the activity of hepatic LDL receptors, which remove LDL from plasma through receptor-mediated endocytosis (3,5,7).…”

mentioning

confidence: 99%

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Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits.

Patrick¹,

Gil²,

Südhof³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

292

124

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Through the use of a quantitative solution hybridization assay with 32P-labeled cDNA probes, we found that mevinolin, an inhibitor of cholesterol synthesis, elevates the level of mRNA for the low density lipoprotein receptor in livers of hamsters and rabbits. In hamsters the maximal effect (3-fold increase) occurred at 0.1% mevinolin in the diet for 10 days. The same dose produced a maximal induction (10-fold) of mRNA levels for 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme of cholesterol synthesis, and a maximal decrease (80%) in plasma cholesterol. The drug lowered the level of all cholesterol-carrying lipoproteins in plasma. In normal rabbits, mevinolin produced a 90% reduction in plasma low density lipoprotein-cholesterol levels, which was associated with a 2.5-fold increase in low density lipoprotein receptor mRNA levels. A similar induction of receptor mRNA occurred in livers of Watanabe-heritable hyperlipidemic rabbits, although the plasma cholesterol was not reduced to normal, presumably because the receptors produced by the mutant mRNA function poorly. These data are consistent with the hypothesis that mevinolin and other inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase lower plasma cholesterol levels in part by stimulating production of mRNA for the low density lipoprotein receptor in liver.

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“…Most statins are similar in structure to the enzyme's substrate, HMG-CoA, and act as competitive inhibitors. Inhibition of this enzyme by statins translates into lowering low density lipoprotein (LDL)-cholesterol via enhanced LDL receptor expression (3,4). As high LDL levels are causally associated with increased cardiovascular disease (CVD), statin treatment is effective in the primary and secondary prevention of CVD that is generally safe and well tolerated (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: A prospective, observational 56-month follow-up study

Duvnjak

Blaslov

2016

Journal of Clinical Lipidology

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Effectiveness of mevinolin on plasma lipoprotein concentrations in type II hyperlipoproteinemia

Cited by 86 publications

References 16 publications

Effect of low density lipoproteins, high density lipoproteins, and cholesterol on apolipoprotein A‐I mRNA in Hep G2 cells

Effect of low density lipoproteins, high density lipoproteins, and cholesterol on apolipoprotein A‐I mRNA in Hep G2 cells

Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in livers of hamsters and rabbits.

Statin treatment is associated with insulin sensitivity decrease in type 1 diabetes mellitus: A prospective, observational 56-month follow-up study

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